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Anyone transporting powders, granulates or pellets via pneumatic systems will sooner or later encounter the dosing gate — also known as a rotary valve, rotary airlock or rotating valve. This compact device plays a crucial role in every powder processing installation: it provides controlled transfer of bulk goods between spaces of different pressure, without losing the airflow.

For process engineers and production managers in pharma, fine chemicals, food and battery production, choosing the right dosing gate directly affects process stability, production loss and installation safety.

How does a dosing gate work?

A dosing gate consists of a rotor with cells (vanes) that rotates within a cylindrical housing. The principle is simple but effective:

1. Filling — material drops through the inlet into the rotor's cells
2. Transport — the rotor turns and carries the material to the outlet
3. Discharge — the material drops or is blown into the receiving system

Rotation speed determines dosing accuracy: slower = less material per unit of time. This makes the dosing gate suitable for both continuous processes and precise batch dosing.

Because the rotor seals off the space between the high- and low-pressure sides, the pressure difference remains intact. This is essential in pneumatic transport, where the transport air would otherwise escape via the material stream.

Types of dosing gates

Not every dosing gate is suitable for every application. The main variants:

Standard dosing gate (open rotor)

For dry, free-flowing materials without high hygiene requirements. Suitable for granulates, pellets and non-sticky powders in the chemical industry.

GMP dosing gate (hygienic design)

Fully cleanable (CIP/SIP), polished surfaces, no dead zones. Required for pharma, food and nutraceuticals. Complies with FDA and EHEDG standards.

ATEX dosing gate

For explosion-sensitive powders (St1–St3) in zones 20, 21 or 22. Fitted with an explosion-proof motor, grounding and spark-free materials. Mandatory for flammable powders such as fine metal dust, pigments or certain food products.

Containment dosing gate (closed system)

For products with a low exposure limit (OEL < 1 µg/m³). Equipped with a mechanical seal to fully prevent dust emission. Applicable to APIs, cytostatics and hormones.

High-temperature dosing gate

For hot gases, drying processes or high-temperature pneumatic transport. Housing and rotor are made of heat-resistant steel.

Applications by sector

Pharma and API production: Dosing gates are used for transferring active substances between dryer, mill and packaging. Containment versions with SMEPAC validation are standard for OEB 3–5 products.

Fine chemicals and ATEX environments: Pigments, catalysts and fine chemicals require ATEX compliance. The dosing gate acts as a pressure-resistant transition in the pneumatic transport system.

Food and nutraceuticals: Sugars, proteins, herbs and vitamins are hygienically transferred via GMP dosing gates with CIP capability. The installation complies with EHEDG and FDA standards.

Battery production: Lithium salts (LiPF6) and cathode material (NMC, LFP) are moisture- and oxygen-sensitive. The dosing gate is fitted with an inert gas seal and ATEX Zone 21 certification.

Plastics and polymer processing: Granulates and pellets are precisely dosed into extruders and mixing installations via dosing gates, with minimal particle damage.

What to consider when choosing a dosing gate?

Several parameters play a role in selecting a dosing gate: bulk density and flow properties of the material, desired throughput capacity (kg/h or m³/h), pressure difference across the gate (bar), ATEX requirement (zone and dust class), hygienic design (CIP/SIP), wear resistance for abrasive material and the required containment level (OEL class).

An incorrectly chosen dosing gate leads to wear, leakage, product loss or — in the worst case — a safety incident. Hecht Technology always advises based on product analysis and process parameters.

Hecht Technology: integrated dosing gate solutions

Hecht Technology supplies and integrates dosing gates as part of a complete powder handling system. From pneumatic transport to containment filtration: the dosing gate is matched to the product, the pressure difference and the safety requirements of your installation.

More information about dosing gates and rotary valves is available at hecht-technology.nl and hecht.eu.

Conclusion

A dosing gate is an indispensable link in every powder processing installation with pneumatic transport. The right version — GMP, ATEX or containment — determines the safety, accuracy and cleanability of your process. Choose based on product characteristics and process parameters, not on price alone.

Want to know more? Visit hecht-technology.nl or get in touch directly.

Our products

• Dosing gate

Moving powders through a plant looks simple, but in practice it is a source of dust, product loss, segregation and physical strain. Vacuum transport solves these problems by moving powder in a closed, dust-free way using negative pressure. For engineers, buyers and QA in pharma, chemicals, food and the battery industry, vacuum technology offers a hygienic, safe and flexible way to move bulk materials through the process. HECHT designs vacuum transport systems matched to your product and layout.

How vacuum transport works

Vacuum transport moves powder through a closed pipeline using a vacuum pump that creates negative pressure at the end. The powder is drawn in at the pick-up point, carried in the air stream and separated from the air in a receiver. The air is filtered and discharged; the powder drops through a valve into the next process step.

Because the system operates under negative pressure, no dust escapes in the event of a leak — air is drawn inward instead. This makes vacuum transport inherently safer than transport under positive pressure.

The core components of a vacuum system

A reliable vacuum transport system consists of matched components.

• Pick-up point — lance, hopper or suction nozzle that takes the powder from a bag, big bag or container
• Transport line — smooth, earthed pipe or hose that guides the powder without loss
• Receiver — vacuum separator in which powder and air are separated
• Filter unit — cartridge or bag filter that removes fine dust from the exhaust air
• Vacuum generator — pump or venturi that delivers the required negative pressure
• Outlet valve — valve that passes the powder in metered fashion to the next step

Advantages over mechanical transport

Mechanical transport systems such as screws and conveyor belts have moving parts in contact with the product, bringing wear, cleaning and contamination issues. Vacuum transport offers structural advantages.

• Dust-free — fully closed transport protects operators and the environment
• Hygienic — smooth, cleanable pipes without dead spots, suitable for GMP and EHEDG
• Flexible — pipes follow any route through the plant, including vertical runs
• Product-friendly — controlled velocity limits particle breakage and segregation

Applications in the process industry

Vacuum transport suits a wide range of powders and processes.

• Pharma — transport of APIs and excipients under containment, with validation to GMP
• Chemicals — moving pigments, catalysts and additives, often in ATEX environments
• Food — hygienic transport of milk powder, cocoa, flour and spices
• Battery — transfer of cathode and anode powders under inert, moisture-free conditions

Containment and operator protection

For highly active substances, vacuum transport is a natural containment strategy. Because the powder is never exposed to open air, operator exposure is minimal. Combined with split butterfly valves at pick-up and discharge points, a vacuum system can meet high OEB classes.

Containment performance is verified to SMEPAC, giving you objective exposure figures. For combustible powders the system is earthed and built ATEX-compliant, optionally with nitrogen inerting.

Design factors that determine performance

The performance of a vacuum system depends on correct sizing. An undersized system clogs; an oversized system wastes energy and can damage powder.

• Product properties — density, particle size, flowability and moisture sensitivity
• Transport distance and height — determine the required negative pressure and air flow
• Throughput — required capacity in kilograms per hour
• Cycle time — continuous or batch, depending on the downstream process

HECHT determines these parameters through product analysis and, where needed, transport trials in its own test centre.

Frequently asked questions about vacuum transport

Why is vacuum transport safer than pressure transport?

Under negative pressure, air is drawn inward, not blown outward. In a leak, no dust is released, protecting operators and the environment.

What distances can vacuum transport cover?

Depending on product and system, distances of several tens of metres horizontally and vertically are achievable.

Does vacuum transport damage the product?

With correct sizing and velocity control, particle breakage is minimal; HECHT matches air velocity to breakage sensitivity.

Is vacuum transport suitable for highly active substances?

Yes, combined with split butterfly valves and SMEPAC-verified containment it suits high OEB classes.

How is the system cleaned?

Via WIP or CIP, depending on the version, so cleaning takes place without disassembly and reproducibly.

How do I choose a vacuum transport system for pharmaceutical powders?

Match the system to the OEB classification of your substance: standard vacuum conveying suits low-potency excipients (OEB 1 to 3), while high-potency APIs (OEB 4 to 6) require containment-integrated vacuum transport with split-valve or isolator connections and SMEPAC-validated performance.

Related guides

• Screw conveying
• Pressure vessels
• Vacuum deaerators
• Industrial filtration

Tailored advice from HECHT

A vacuum system that fits your product starts with a thorough analysis of your powder, distance and throughput. HECHT sizes, tests and supplies vacuum transport that is dust-free, hygienic and safe, and that integrates seamlessly with your dosing and filling systems. Contact us for a transport analysis and a tailored system proposal.

Our products

• Double cone vacuum dryers
• Conical vacuum dryers

The CTD dossier: universal structure for registration

The Common Technical Document (CTD) is the harmonised dossier structure used worldwide for drug registration with the EMA, FDA, Health Canada and more than 40 other regulators. The CTD consists of five modules: Module 1 (regional administrative information), Module 2 (summaries and overviews), Module 3 (quality data), Module 4 (preclinical data) and Module 5 (clinical data). Module 3 contains all pharmaceutical quality data: API specifications, formulation design, manufacturing method, validation data and stability studies. Electronic submission (eCTD) is mandatory with the FDA, EMA and various other authorities; eCTD software ensures correct XML structure and lifecycle management of the dossier.

EMA registration procedures in Europe

Four registration procedures are available in Europe: the centralised procedure (CP) via the EMA grants a Marketing Authorisation valid across all EU/EEA member states; the decentralised procedure (DCP) and the mutual recognition procedure (MRP) run via national authorities of multiple member states; the national procedure applies to registration in a single country. Biologics, oncology products and HIV medicines are required to use the CP; for other medicines the CP is optional but offers efficiency. EMA assessment time is a maximum of 210 active assessment days (with clock-stop periods excluded, typically 12-18 months total). PRIME (Priority Medicines) offers accelerated assessment for products with major therapeutic benefit for a condition without adequate treatment options.

FDA NDA and ANDA: US registration

In the US, innovative medicines are registered via a New Drug Application (NDA) under 21 CFR Part 314. FDA review time for a standard NDA is 10 months, for Priority Review (serious conditions) 6 months. Important FDA expedited designations are: Fast Track, Breakthrough Therapy, Accelerated Approval and Priority Review. The Prescription Drug User Fee Act (PDUFA) funds FDA review capacity through annual fees from manufacturers; the PDUFA fee for an NDA is approximately 4 million dollars. Pre-submission meetings (Type A, B, C) with the FDA are strategically valuable to reach alignment on clinical programme design, endpoints and the registration plan.

Orphan drug and breakthrough therapy designations

Orphan Drug Designation (ODD) offers incentives for medicines targeting rare conditions (fewer than 5 per 10,000 in Europe; fewer than 200,000 patients in the US): 10 years of market exclusivity (EU) or 7 years (US), reduced registration fees and development guidance. Breakthrough Therapy Designation at the FDA is intended for products with preliminary clinical evidence of substantial benefit versus existing therapy; it offers intensive FDA guidance and can lead to accelerated approval based on surrogate endpoints. The EMA equivalent PRIME (Priority Medicines) offers comparable benefits in Europe. Combining designations maximises the chance of an efficient, patient-focused development route.

Post-approval changes and variations

After market authorisation, changes to manufacturing, specifications, formulation or site require formal notification or approval via the variation procedure system. In Europe, variations are classified as Type IA (minor, 30-day notification), Type IB (minor, 30-day approval), Type II (major, 60-day review) and extensions (Major Change). The FDA distinguishes Prior Approval Supplements (PAS, 6-12 months), Changes Being Effected (CBE-30, 30 days) and Annual Reports. Post-approval change management requires that the impact on product quality be assessed through risk analysis and, if needed, additional studies. SUPAC guidelines (Scale-Up and Post-Approval Changes) provide FDA-specific criteria for which type of supplement is required for manufacturing and formulation changes.

Conclusion

Regulatory strategy and drug registration are complex disciplines requiring in-depth knowledge of international CTD structures, review procedures and post-approval change management. A well-considered regulatory strategy shortens time-to-market and reduces the risk of rejections or additional data requirements. Hecht Technology supports pharmaceutical companies in setting up CTD dossiers, regulatory gap analyses and registration strategies for Europe and the US.

Hecht Technology: process equipment for validation dossiers

A strong registration dossier relies partly on demonstrably validated production equipment. Hecht Technology supplies GMP- and ATEX-certified systems with complete IQ/OQ documentation, such as the single-use isolator, which support the quality substantiation of your CMC dossier for EU and FDA registration.

Our products

• Single-use isolator

Polymorphism: definition and pharmaceutical importance

Polymorphism describes the phenomenon whereby a chemical substance exists in multiple crystalline solid-state forms that share the same molecular composition but differ in their three-dimensional arrangement within the crystal lattice. For pharmaceutical APIs, polymorphism is of critical importance because different crystal forms can differ substantially in solubility, by factors of 2 to more than 100 times, in melting point by up to 30 degrees Celsius, and in physical stability and processability. The best-known example is ritonavir, whose discovery of polymorphic form II in 1998 led to the product being recalled because the new form had 4 times lower solubility and the capsule formulation was no longer therapeutically effective. Pseudo-polymorphs, or solvates and hydrates, are crystal forms in which solvent or water molecules are incorporated into the crystal lattice and likewise exhibit different physicochemical properties. Regulatory authorities require a complete polymorph characterisation report in registration dossiers and control of the polymorphic form in every production batch.

Crystal form screening

Polymorph screening identifies all relevant solid-state forms of an API via systematic crystallisation experiments across a broad range of solvents, temperatures and solvent concentrations. Automated high-throughput screening platforms such as Crystal16 and Crystalline from Technobis crystallise an API under 16 to 96 conditions simultaneously via temperature profiles and antisolvent additions. Screening methods include cooling crystallisation from solvent solutions, antisolvent precipitation, slurry methods in competing solvents, vapour diffusion and mechanochemical grinding of the solid material. Coordinated characterisation of all forms found via XRPD, DSC and TGA at an early stage makes it possible to fully map the polymorphic landscape before registration studies begin. Per project, typically 3 to 15 new crystal forms are found, of which 30 to 50% are pseudo-polymorphic solvates or hydrates in nature and require specific storage conditions.

XRPD and DSC characterisation

X-Ray Powder Diffraction (XRPD) and Differential Scanning Calorimetry (DSC) are the two primary techniques for solid-state characterisation of API crystal forms in pharmaceutical development. XRPD provides a unique diffractogram fingerprint of each crystal form via Bragg reflections at specific 2-theta angles, with the international Cambridge Structural Database (CSD) containing more than 1 million reference structures. Variable-temperature XRPD from 25 to 200 degrees Celsius monitors polymorphic transitions in situ and is essential for understanding the thermodynamic phase diagram of an API. DSC thermograms reveal the enthalpic signatures of phase transitions, melting points and dehydration processes: every endothermic or exothermic peak between 50 and 300 degrees Celsius represents a crystallographically significant event. Thermogravimetric analysis (TGA) combined with DSC distinguishes solvate desolvation from polymorphic transformation by simultaneously measuring weight loss upon heating, with a resolution of 0.1 microgram on modern TGA instruments.

Solubility and stability per form

The intrinsic solubility of different polymorphic forms differs due to the free energy of the crystal lattice and is related via the Ostwald rule of stages: less stable metastable forms have higher solubility. Solubility measurement via the shake flask method at pH 7.4 phosphate buffer distinguishes the thermodynamic solubility of all forms at 37 degrees Celsius in simulated intestinal medium. Metastable forms with higher solubility can create supersaturation in vivo and thereby increase bioavailability, but the risk of spontaneous conversion to the more stable form during processing or storage must be evaluated. Solid-state stability of polymorphs under accelerated storage at 40 degrees Celsius and 75% RH for 3 months shows whether the selected product form remains stable under normal storage conditions. DSC-based thermodynamic stability analysis via the enthalpy-entropy compensation principle can predict the thermodynamic solubility ratio of two polymorphs without experimental solubility measurements.

Polymorph control in manufacturing

Control of the polymorphic form during commercial API manufacturing is a critical quality requirement that must be captured in the control strategy with in-process monitoring and finished-product analysis. In-process control via Raman spectroscopy or NIR monitoring of the crystallisation step detects polymorphic conversion in real time with a response time of 1 to 5 seconds, enabling rapid process intervention. Seeding with the desired polymorphic form at a relative supersaturation of 5 to 15% above the saturation curve initiates crystallisation of exclusively the desired polymorph, achieving a selectivity above 99%. Storage conditions for the API crystallisate and the finished product must be established and specified based on stability studies to prevent polymorphic conversion during long-term storage. XRPD finished-product analysis on every production batch, with a reference diffractogram and acceptance criteria for peak positions within 0.2 degrees 2-theta, is the legal minimum requirement for polymorph control per the Ph.Eur. monograph on API characterisation.

Conclusion

Polymorphism and solid-state characterisation are fundamental aspects of API development that directly affect therapeutic effectiveness, product stability and regulatory acceptance. Hecht Technology supports polymorph screening studies, characterisation and the implementation of polymorph control in API manufacturing processes in accordance with ICH Q6A and Ph.Eur. Contact us for a polymorphism assessment of your API development project.

Our products

• Jett mill

Micro-organisms and cell lines as production platforms

Upstream bioprocessing selects the most suitable production platform based on the desired product, the required post-translational modifications and the production titre. Escherichia coli is the most widely used bacterial expression system due to its rapid growth of 0.3 to 1.0 hour generation time, well-understood genetics and high production titre of over 50 g/L inclusion bodies. Saccharomyces cerevisiae and Pichia pastoris are suitable yeast expression systems for proteins requiring secretion or N-glycosylation, with titres of 3 to 10 g/L for simple proteins. Mammalian cell lines, with CHO (Chinese Hamster Ovary) as the dominant choice for more than 70% of approved biologics, offer correct human-like glycosylation for therapeutic proteins. Insect cell systems Sf9 and High Five via baculovirus infection and transient expression systems offer flexibility for small batches and rapid titre improvement in the early development phase. The production platform directly determines the upstream and downstream processing strategy across the full life cycle of the drug.

Bioreactor design and mixing

Bioreactor design is critical for controlling the cells' environmental conditions and optimising the mass transfer of oxygen and carbon dioxide. Stirred tank reactors (STR) are the most widely used bioreactor type in pharmaceutical production, with working volumes from 2 to over 25,000 litres, fitted with Rushton turbine or marine propeller impellers at an impeller-to-vessel diameter ratio of 1:3. The bioreactor's volumetric oxygen transfer coefficient (kLa) determines the maximum oxygen supply capacity of the culture: for CHO cells with a specific oxygen consumption qO2 of 1 to 10 mmol O2/g·h, a kLa of 2 to 20 h⁻¹ is required. Airlift bioreactors without mechanical agitation use air or gas bubbles for mixing and are suitable for shear-sensitive cell lines, where the Kolmogorov length scale of turbulence must remain above the cell diameter of 10 to 20 micrometres. Disposable bioreactors made from single-use materials offer advantages for clinical batch production: no cleaning, elimination of cross-contamination and faster turnaround between batches of 4 to 6 hours versus 48 to 72 hours for stainless steel.

Fed-batch and continuous fermentation

Fed-batch cultivation is the dominant process mode in pharmaceutical bioproduction and combines the benefits of high cell concentration with controllable product formation via a guided feed addition protocol. The fed components, typically glucose, amino acids and vitamins, are dosed based on online measurements of the glucose concentration below 1 g/L via enzymatic or NIR sensors to avoid overfeeding and catabolite repression. Fed-batch CHO cell cultures reach cell concentrations of 50 to over 100 million cells per mL and monoclonal antibody titres of 3 to over 10 g/L over process durations of 12 to 21 days. Continuous fermentation via perfusion culture circulates cell retention through a spin filter or alternating tangential flow filtration (ATF), with cell concentrations up to 200 million cells per mL and day-for-day productivity up to 3 times higher than fed-batch. Intensified bioprocessing via N-1 perfusion at the seed fermentation stage compensates for the longer start-up phase of production bioreactors and increases the facility's total annual productivity by 25 to 50%.

Process control: pH, DO and glucose

Process control in bioreactors monitors and regulates critical process parameters that directly affect cell growth and product formation via closed-loop control strategies. Dissolved oxygen (DO) control via a cascade controller to impeller speed and air supply maintains oxygen saturation between 30 and 50% of air saturation for optimal aerobic CHO cell culture; under-saturation below 20% causes metabolic stress and reduced productivity. pH control via addition of sodium carbonate solution or CO2 gassing maintains pH within 0.05 units of the setpoint of 6.95 to 7.20, depending on the cell line and desired metabolic profile. Glucose concentration measurement via an online YSI analyser or enzymatic flow cell with a response time of 5 to 15 minutes drives the fed-batch feed pumps and prevents glucose limitation at concentrations below 0.5 g/L. Process analytical technology (PAT) via online dielectric spectroscopy biomass sensor provides direct measurement of viable cell concentration every 15 seconds without sampling loss, enabling continuous process optimisation.

Bioreactor scale-up

Scaling up from 2-litre lab scale to 200-litre pilot scale and 10,000-litre commercial scale requires preserving critical bioprocess parameters via dimensionless numbers and specific scaling criteria. Equal specific mixing or power input per volume (P/V) of 50 to 200 W/m³ is a common scaling criterion that ensures the turbulent micro-scale stays above the cell diameter to limit shear stress. Gas sparging via injection nozzles and ring spargers must be scaled based on equal gas holdup fraction, which amounts to 0.01 to 0.05 v/v, measured via the pressure differential method. Heat transfer calculations for biological heat generation (qheat) of 50 to 200 kW/m³ determine the cooling water requirements of the jacketed bioreactor at production scale. Volumetric production time (PT) of the bioreactor, defined as the annual production hours divided by the working volume, is a key parameter for comparing the economic efficiency of different bioreactor formats at comparable capital and operational costs.

Conclusion

Upstream bioprocessing is the technological foundation for the production of biologics, monoclonal antibodies and biotechnological medicines that are transforming the pharmaceutical industry. Hecht Technology provides expertise in bioreactor design, process control implementation, fed-batch optimisation and scale-up for biotechnological production processes. Contact us for support with your upstream bioprocessing project.

What do industrial fermentation facilities and GMP qualification cost?

Investment in a fermentation facility typically consists of CapEx (bioreactor, HVAC, sterilisation, monitoring, utilities) of approximately 1 to 5 million euros, OpEx of 500,000 to 2 million euros per year, and GMP validation costs of 200,000 to 1 million euros. For biologics with an annual market of 5 to 20 million euros, ROI is typically 3 to 5 years. Incremental scale-up — pilot, clinical, commercial — spreads the investment risk across the development phases.

Hecht Technology: single-use and containment in bioprocessing

Modern upstream bioprocessing increasingly employs single-use technology to prevent cross-contamination between batches and reduce validation time. Hecht Technology's single-use isolator supports this for contained transfer and sampling of biomass and media, while our columns and process towers are used for downstream separation and purification steps after fermentation.

Our products

• Single-use isolator
• Columns and process towers

What is controlled release?

Controlled release (CR) is a pharmaceutical formulation strategy in which the active substance is not released immediately after intake, but dosed over time or at a specific location in the body. The goal: more stable plasma concentrations, fewer side effects, lower dosing frequency and improved treatment adherence. Synonymous terms include modified release (MR), sustained release (SR), extended release (ER) and delayed release (DR) — each with a specific meaning in the pharmacopoeia.

Types of modified release formulations

Extended release (ER/SR)

The active substance is released over 8–24 hours. Peak plasma concentrations are reduced, troughs are raised — ideal for APIs with a narrow therapeutic index (carbamazepine, metformin, nifedipine). Mechanism: diffusion through a matrix polymer or membrane, erosion of a matrix, or osmotic drive.

Delayed release (DR)

Release is delayed until a specific location in the gastrointestinal tract — typically the small intestine or colon. Enteric coating is the best-known example: the coating dissolves at pH >5.5 (small intestine) and protects gastric-irritating APIs or acid-labile biologics.

Pulsatile release

Multiple release moments over time, triggered by colon bacteria (polysaccharide coatings), pH switches or pressure-sensitive systems. Application: chronopharmacology (antihypertensives for nocturnal blood pressure peaks).

Targeted release

Release at specific anatomical locations via ligand-receptor binding (nanoparticles with targeting ligands), mucoadhesion or local implants. Strongly growing segment driven by oncology and biologics.

Technology platforms for controlled release

Matrix tablets

The API is embedded in a polymer matrix (HPMC, ethylcellulose, Carbopol). Release via diffusion through the matrix and/or erosion of the polymer. Simple to produce via direct compression or granulation. Most widely used CR platform for oral solid dosage forms.

Reservoir systems

An API core surrounded by a rate-limiting membrane coating (ethylcellulose, Eudragit RS/RL). Release rate determined by membrane thickness and pore properties. Higher production precision required, but excellent release control.

Osmotic systems (OROS)

The OROS tablet (Alzet-type) uses osmotic pressure as the driving force: water penetrates through a semipermeable coating, builds up pressure and pushes the API out through a laser-drilled orifice. Release rate is near zero-order — virtually independent of GI motility and pH. High manufacturing precision required (laser orifice, coating thickness).

Lipid-based systems

Wax matrices (carnauba wax, beeswax, glyceryl behenate) for low-solubility APIs. Release via lipase-driven erosion. Applied to lipophilic APIs that are poorly soluble in aqueous media.

Regulatory aspects: IVIVC and bioequivalence

For modified release products, the FDA and EMA require an In Vitro-In Vivo Correlation (IVIVC) — a mathematical relationship between the in vitro release profile (dissolution) and in vivo pharmacokinetics. A level A IVIVC (point-to-point correlation) makes it possible to justify formulation changes without new clinical studies. Bioequivalence studies for CR products generally include tests in the fed and fasted state.

Manufacturing challenges

Controlled release places higher demands on process control than immediate release. Coating uniformity (standard deviation <3% weight gain per tablet), polymer concentration and drying conditions determine the release profile. Scale-up from lab to production is critical: fluid bed coaters and perforated pan coaters behave differently at large scale. Containment is an additional challenge for CR formulations of highly potent APIs — combining coating equipment with an isolator or RABS integration.

Conclusion

Controlled release technology is one of the most valuable tools in pharmaceutical formulation development: better therapeutic profile, higher patient compliance and extended product life cycle. The choice of the right platform depends on API properties, desired release profile, production capacity and regulatory strategy.

More about pharmaceutical manufacturing engineering: hecht-technology.nl.

Hecht Technology: particle size precision for modified release

Controlled release depends on a precisely defined particle size distribution of the API and excipients. Hecht Technology's Jett Mill enables reproducible, accurate particle size reduction — a critical process parameter in the development and manufacture of modified-release formulations.

Our products

• Jett mill

Nanoparticles as a drug delivery platform

Nanoparticulate drug delivery systems are particles of 10–1000 nm that transport, protect and release APIs in a controlled manner at the desired location. The promise of nanoformulations is significant: improved drug solubility, extended circulation time, active tumour targeting and minimisation of systemic side effects. The mRNA vaccines from Pfizer/BioNTech and Moderna have given lipid nanoparticles (LNP) worldwide recognition as a manufacturing platform.

Liposomes: the oldest nanoplatform

Liposomes are spherical vesicles of one or more phospholipid bilayers enclosing an aqueous compartment. Hydrophilic APIs are encapsulated in the internal aqueous space; lipophilic APIs in the lipid bilayer. First FDA-approved liposome: Doxil (liposomal doxorubicin) in 1995.

Critical quality attributes of liposomes:

• Particle size (Z-average): typically 80–200 nm, measured via DLS
• Polydispersity index (PDI): <0.2 for a homogeneous population
• Zeta potential: indicator of stability; >+30 or <-30 mV for electrostatic stabilisation
• Encapsulation efficiency (EE%): percentage of API incorporated in the liposome vs. total added

Lipid nanoparticles (LNP): the mRNA revolution

LNPs are the most widely used formulation for nucleic acid delivery (mRNA, siRNA, ASO). Four lipid components work together:

• Ionisable lipid: positively charged at low pH (mRNA encapsulation) and neutral at physiological pH (reduced toxicity). Examples: DLin-MC3-DMA (Patisiran/Onpattro), SM-102 (Spikevax), ALC-0315 (Comirnaty)
• Helper lipid (DSPC/DPPC): structural stability of the lipid bilayer
• Cholesterol: membrane rigidity and fusogenicity
• PEG-lipid: steric stabilisation, extended circulation time, reduced MPS uptake

LNP production via microfluidics or T-junction mixing: the organic phase (lipids in ethanol) and aqueous phase (mRNA in acetate buffer) are mixed under a controlled flow ratio. Instantaneous nanoprecipitation yields LNPs of 80–120 nm.

Polymeric nanoparticles and micelles

PLGA (poly-lactic-co-glycolic acid) nanoparticles are the most studied biodegradable polymeric nanocarriers. PLGA hydrolyses in vivo into lactic acid and glycolic acid and is approved by the FDA/EMA as an excipient. Production via nanoprecipitation, emulsification-diffusion or double emulsion methods.

Polymeric micelles (block copolymer aggregates of 20–100 nm) are suitable for hydrophobic APIs dissolved in the micellar core. Advantage: small particle size, low critical micelle concentration, passive tumour targeting via the EPR effect.

GMP manufacturing of nanoformulations

Nanoformulations place special demands on GMP manufacturing: sterile filtration is not possible for liposomes and LNPs >200 nm (0.22 µm filters block particles that large); aseptic processing is then required. Scale-up from lab microfluidics to commercial production (Spark NanoAssemblr, Precision NanoSystems) is an active area of development.

Conclusion

Nanoparticulate drug delivery has grown from a laboratory curiosity into a clinically and commercially proven technology platform. Liposomes, LNPs and polymeric nanoparticles offer unprecedented possibilities for targeting and API protection — with accompanying manufacturing challenges in scale-up, sterile processing and characterisation.

More about biopharma manufacturing engineering: hecht-technology.nl.

Our products

• Jett mill
• Single-use isolator

What is a Dry Powder Inhaler (DPI)?

A Dry Powder Inhaler (DPI) is an inhalation device that delivers dry powder directly into the lungs without a propellant. The patient activates the dose by inhaling: the airflow through the device deagglomerates the powder and transports the active particles to the bronchioles and alveoli. DPI systems are widely used for asthma, COPD and lung infections (including inhaled antibiotics and vaccines).

The success of a DPI stands or falls with formulation and manufacturing process. Particle size, carrier particles, blend uniformity and moisture sensitivity together determine the Fine Particle Fraction (FPF) — the proportion of the dose that actually reaches the lungs.

The pharmacology of inhalation: why particle size determines everything

Only particles of 1–5 µm reach the deeper lung regions (bronchioles, alveoli). Larger particles (>10 µm) deposit in the oropharynx and are pharmacologically inactive. Particles <1 µm are exhaled. The aerodynamic particle size (MMAD, Mass Median Aerodynamic Diameter) is therefore the most critical quality parameter for inhalation formulations, measured via cascade impactor (NGI, Andersen).

DPI formulation strategy

Carrier-based formulation

The most widely used DPI formulation strategy combines fine API particles (1–5 µm) with coarse carrier particles of lactose (50–200 µm). The API adheres to the surface of the carrier and is released upon inhalation by turbulence within the device. Critical parameters:

• Lactose quality: morphology, specific surface area and moisture content determine API-carrier interaction
• Lactose fines fraction: small lactose particles (fines, <10 µm) compete with the API for carrier surface and improve the FPF
• Mixing order and intensity: determine adhesion uniformity and avoid excessive deagglomeration during production

Carrier-free formulation

For highly potent APIs or when no suitable carrier is available, carrier-free formulations are used: spray-dried or lyophilised porous particles with low density and aerodynamically favourable morphology. Higher production complexity, but superior FPF (up to >60%).

Micronisation and particle production

API micronisation for DPI formulation requires particle size control at sub-5µm level. Common methods:

• Jet milling (fluidised bed jet mill): air- or nitrogen-driven interparticle collisions, no thermal load, scalable to production volume
• Spray drying: solution or suspension evaporated in a hot air stream, produces spherical particles with controllable size and morphology
• Supercritical fluids (RESS, SAS): niche application for polymorph-sensitive APIs

Containment during micronisation of HPAPIs (OEB 4–5) is a critical engineering requirement: closed mills with integrated filter separation and negative pressure are standard for potent inhalation APIs.

Blend uniformity and mixing

DPI blends require extreme uniformity: Content Uniformity (CU) specifications of <5% RSD at dose level are common. This places high demands on:

• Deagglomeration of micronised material before mixing (via sieving or sonication)
• Mixing equipment (tumble blender, bin blender) and mixing parameters (rpm, fill degree, mixing time)
• Electrostatic charge management (use of grounded equipment, anti-static liners)

Moisture sensitivity and packaging

Inhalation powders are extremely moisture-sensitive: even at 40–60% RH, lactose-based blends can sinter or API crystallisation can occur, dramatically reducing FPF. Production under controlled conditions (RH <30%, T 20–22°C) and packaging in moisture-resistant blister packs (aluminium-aluminium) or capsules with desiccant are standard GMP practice.

Regulatory requirements and quality control

DPI products are characterised via: Aerodynamic Particle Size Distribution (APSD) via NGI, Fine Particle Fraction (FPF), Delivered Dose Uniformity, MMAD and GSD. ICH Q4B Annex 9 and EMA/FDA inhalation guidelines describe test methods and acceptance criteria. Device-formulation combination testing is mandatory for registration.

Conclusion

DPI formulation is one of the most complex areas in pharmaceutical product development. Particle size, carrier interaction, micronisation process, blend uniformity and moisture control must all be optimised simultaneously for a robust product. The process steps require specialised equipment for both production and containment.

More about inhalation powders and DPI production equipment: hecht-technology.nl.

Our products

• Jett mill
• Single-use isolator

Bag filter or cartridge filter: the choice determines efficiency, maintenance and TCO

Bag filters and cartridge filters are both effective technologies for industrial dust separation, but they perform fundamentally differently with different dust types, particle sizes and process requirements. The wrong choice leads to increased maintenance frequency, excessive pressure drop or insufficient separation efficiency. A good selection guide starts with understanding filter operation and ends with Total Cost of Ownership.

Operating principle: how bag filters and cartridge filters separate dust

A bag filter (baghouse filter) uses long, cylindrical filter sleeves of woven or felted fabric. The dust-laden gas flows through the inside or outside of the bag, depending on the design. Dust adheres to the filter medium and forms a cake that actually increases filtration efficiency (primary filtration via the dust cake). Cleaning takes place via compressed air pulse-jet or mechanical shaking.

A cartridge filter uses pleated filter media — typically polyester, cellulose or PTFE — with a large filter surface area in a compact volume. The pleated structure provides 10 to 30× more filter surface per unit volume than a bag filter. Pulse-jet cleaning is standard.

When do you choose a bag filter?

• High dust concentrations (>5 g/m³): bag filters are designed for heavy dust loads and quickly form an efficient dust cake
• Coarse, abrasive particles (>10 µm): the robust fabric material withstands wear better than pleated cartridges
• Moist or sticky dust types: some fabric types (PTFE membrane) are better suited to sticky dust that would clog cartridges
• High-temperature processes (up to 260°C): fibreglass or PTFE bags are available for high-temperature applications
• Large volume flows: bag filters scale up more efficiently to large gas volumes

When do you choose a cartridge filter?

• Fine, dry dust types (<10 µm): cartridges offer higher filtration surface area and a lower A/C ratio for fine dust
• Low to moderate dust concentrations (<5 g/m³): cartridges are less suitable for heavy dust loads
• Limited installation space: the compact design fits into tight machine rooms or production floors
• Pharmaceutical and food applications: FDA-compliant filter material grades available, easier to clean and validate
• Frequent filter changeover: cartridges are quicker to replace than bags

Comparison overview: bag filter vs. cartridge filter

• Filter surface area per volume: cartridge filter > bag filter
• Suitable for high dust loads: bag filter > cartridge filter
• Compactness: cartridge filter > bag filter
• Temperature resistance: bag filter (specialised versions) > cartridge filter
• GMP cleanability: cartridge filter (easier) > bag filter
• Investment cost: comparable, depending on material and scale

Hecht Technology supplies both bag filters and cartridge filters for industrial dust separation in pharma, chemistry, food and the battery industry. More information: hecht-technology.nl.

Read also

• The different types of bag discharge systems and their applications
• The importance of integrated filters in bag discharge installations
• Benefits of mobile bag discharge installations for flexible production
• SE-H bag dumping cabinet

Why automation matters in bulk handling

As production lines handle more product variants at higher volumes and under stricter regulation, manual bulk handling reaches its limits. Automation brings repeatability, safety and traceability: every dosing step, transfer and batch is controlled, logged and reproducible. For powder and bulk processes in pharma, food and chemicals, a well-designed control architecture is the difference between a line that reliably meets its throughput and compliance targets and one that depends on operator experience alone.

PLC control: the backbone of automated bulk handling

The Programmable Logic Controller (PLC) is the real-time engine of the installation. It reads sensors — level, weight, pressure, position — and drives valves, rotary locks, screw feeders and conveying systems in precisely timed sequences. A robust PLC program enforces interlocks that prevent unsafe states, such as opening a discharge valve before the receiving vessel is ready. Because the PLC executes deterministically, it delivers the same result batch after batch, which is essential for both safety and product quality.

SCADA and HMI: visualisation and supervisory control

Where the PLC executes, SCADA (Supervisory Control and Data Acquisition) and the HMI (Human-Machine Interface) let people see and steer the process. Operators monitor live status, start and stop sequences, adjust setpoints and respond to alarms from a single screen. SCADA also aggregates data across multiple machines and lines, giving production managers a real-time overview of throughput, availability and deviations.

Recipe management and flexible production

Modern bulk handling rarely makes a single product. Recipe management stores the parameters for each product — dosing quantities, sequence, mixing time, tolerances — and loads them at the push of a button. This shortens changeovers, eliminates transcription errors and lets one line switch safely between formulations while keeping every recipe version under control.

Traceability and data integrity in regulated production

In GMP and food-safety environments it is not enough to make the product correctly; you must be able to prove it. Automated systems capture batch records automatically: which materials, which quantities, which equipment, which operator, at what time. Compliance with standards such as FDA 21 CFR Part 11 requires audit trails, access control and tamper-evident data. Building data integrity into the control system from the start turns compliance from a paperwork burden into an automatic by-product of running the line.

Industry 4.0 and digital bulk handling

Connecting the control layer to higher-level systems — MES, ERP and cloud analytics — unlocks the next step. Condition monitoring predicts wear before it causes downtime, energy data reveals optimisation potential, and production data flows straight into planning. Hecht Technology designs automation architectures that are secure, scalable and built around your process, so your bulk handling line is ready for both current requirements and continuous improvement.

Related guides and solutions

• Dosing and weighing technology
• Pneumatic powder transport
• Pharmaceutical powder handling and GMP
• Bulk handling
• Big bag handling

Hecht Technology: automation-ready bulk handling systems

PLC and SCADA integration is only effective when the underlying equipment is genuinely designed for it. Hecht Technology's filling stations and dosing systems come standard-prepared for automation and batch registration, with load cells, sensors and ICS connections that integrate seamlessly with your existing PLC/SCADA environment for full traceability.

Our products

• BG big-bag filling station
• Feeding screw

Granulation: from powder to processable granulate

Granulation is the process in which fine powder particles are combined into larger, stable agglomerates (granules). The goal is to improve the processing properties of the powder: better flowability for dosing systems and tablet presses, higher bulk density for more compact storage and transport, improved compressibility for tableting, and reduced dust formation with hazardous substances. Granulation is a central step in pharmaceutical solid dosage form production and is also applied in food, chemistry and fertiliser production.

Wet granulation: the most widely used granulation technique

In wet granulation, powder particles are combined by adding a binder solution (granulation liquid). The binder (gelatine, PVP, HPMC, hydroxypropyl cellulose) forms bridges between particles that yield stable granules after drying. Wet granulation takes place in:

• High-shear mixer-granulator: intensive mixing and granulation in a single vessel; short process time (10–20 min); suitable for APIs requiring robust granulation
• Fluid bed granulator: powder is suspended in a fluidised bed while binder solution is sprayed on; gentler process; simultaneous granulation and drying
• Twin-screw granulator: continuous processing; high formulation flexibility; suitable for continuous manufacturing lines

Wet granulation is not suitable for moisture-sensitive or thermolabile APIs.

Dry granulation: for moisture-sensitive products

In dry granulation, powder particles are compressed together without adding liquid. The two most commonly used methods are:

• Roller compaction: powder is compressed between two counter-rotating rollers into compact ribbons, which are then milled into granulate. Scalable, continuous processing, broadly applicable
• Slugging: powder is first compressed into large tablets (slugs) and then milled. Less efficient than roller compaction; increasingly less used

Fluid bed technology: granulating and drying in one step

Fluid bed processors can granulate, coat and dry in the same equipment. An upward airflow keeps the material suspended while a spray nozzle applies binder or coating. Fluid bed technology offers high process flexibility but requires precise control of air volume flow, temperature and spray rate.

Selection criteria for granulation technology

• Moisture sensitivity of the API: moisture-sensitive → dry granulation or fluid bed
• Thermolability: thermolabile → low-temperature fluid bed or dry granulation
• Batch vs. continuous production: continuous production → twin-screw or roller compaction
• Desired granule properties: particle size, density, porosity
• Scale: from gram-scale lab to ton-scale production

Hecht Technology supplies bulk handling systems for granulate processing lines: contained transfer, dosing and transport of granulates for pharma and food. More information: hecht-technology.nl.

Hecht Technology: downstream processing after granulation

After granulation, the granulate often still needs to be dried and brought to the correct particle size. Hecht Technology supplies Nutsche filter dryers for drying moist granulates in a closed, GMP-compliant environment, and the Jett Mill for fine milling or adjusting the particle size distribution after granulation.

Our products

• Nutsche filter dryers
• Jett mill

Powder characterisation: the key to predictable process behaviour

The properties of a powder determine how it behaves during transport, dosing, mixing, granulation and tableting. Powders with identical chemical composition can be processed fundamentally differently if their particle size, shape, bulk density or flowability differ. Systematic powder characterisation is therefore essential in process design, scale-up and troubleshooting in the pharmaceutical, food and chemical industry.

Particle size distribution (PSD): the most critical powder property

Particle Size Distribution (PSD) describes what percentage of the particles has a given size. PSD directly affects: API dissolution rate, mixing quality, flowability, capsule and tablet fill time, filterability and pneumatic transport behaviour.

Common measurement methods for PSD:

• Laser diffraction: fastest method, measurement range 0.1–3500 µm, wet or dry dispersion, standard in pharma and food
• Sieve analysis: simple, low-cost, suitable for particles >45 µm; less suitable for cohesive powders
• Dynamic image analysis (DIA): also measures particle shape alongside size; valuable for anisotropic particles (needles, flakes)
• Electrical sensing zone method (Coulter counter): high accuracy for narrow distributions in liquid

Bulk density: poured and tapped

Bulk density is measured as poured bulk density and tapped bulk density. The difference between the two provides information about the powder's compressibility. The Carr Index and Hausner Ratio are derived measures:

• Carr Index = (tapped - poured) / tapped × 100%. Values <15% = good flowability, >35% = poor flowability
• Hausner Ratio = tapped / poured. <1.25 = good flow, >1.4 = cohesive powder

Flowability and cohesiveness: process-relevant parameters

A powder's flowability determines whether it flows spontaneously and reproducibly from a silo, hopper or dosing device. Cohesive powders form bridges and rat holes. Measurement methods for flowability include the angle of repose test, the flow function (Jenike shear cell) and dynamic flowability (powder rheometer such as the FT4).

Flow improvers such as silica (Aerosil), magnesium stearate or talc are added to improve cohesive powders — but affect other product properties and generally require formulation validation.

Powder characterisation across the production cycle

Powder characterisation takes place at four points: at procurement (raw material specification), at process design (scale-up from lab to production), during deviation investigation (OOS results or process disruptions) and during regular trending as part of process analytical technology (PAT). Hecht Technology supplies process equipment designed for powders with widely varying characteristic properties. More information: hecht-technology.nl.

Read also

• Powder transport in closed systems 7-step guide
• CIP systems for powder transport: what you need to know
• Bulk handling machine selection
• Powder processing & transport: product overview