Formulation & Process Optimization
Glatt Pharmaceutical Services understands the challenges its clients often encounter in pharmaceutical production, from inconsistent processing conditions to variations in product quality and inefficiencies during scaling, among others. These hurdles can make the transition from lab-scale development to commercial production daunting, and that’s where we step in as a reliable partner.
With decades of experience in formulation, process development, and commercial manufacturing, Glatt Pharmaceutical Services offers its expertise to support clients in optimizing their solid dose formulations and manufacturing processes. When a process needs improvement, we evaluate the existing setup and work closely with you to establish more reproducible processing conditions. By defining the technical requirements for optimal production, we ensure consistent drug product quality—whether in intermediates or final products.
Our team collaborates with clients to refine solid dosage form formulations, if necessary, and optimize the processing scenarios and logistics. This can involve adjusting equipment parameters and improving workflow efficiency, whether at lab scale, pilot scale, or full commercial scale. Once optimized, we help transfer these improved processes and formulations back to your site for seamless integration.
To ensure lasting success, our experts provide hands-on training for your staff, equipping them with the knowledge needed to implement the optimized procedures in their everyday production. By applying a Quality-by-Design philosophy and using Design-of-Experiments (DOE) protocols, Glatt Pharmaceutical Services ensures that the processes and formulations selected are well-justified, robust, and reproducible.
Rather than simply solving problems, Glatt Pharmaceutical Services positions itself as a trusted partner—working alongside its clients to support their journey towards more efficient, scalable, and reliable pharmaceutical production.
Granules and microgranules
Granules are widely used as starting materials for compression into tablets or for filling into capsules.
Low dose APIs can be reliably processed into granules with reproducible content uniformity levels in the final drug product. Variations in API physical properties can be overcome by granulation, resulting in reproducibly compressible materials. The compression characteristics of poorly compressible APIs may be improved by combining them with pharmaceutical excipients in the granulation process, which further improves flowability as well.
Microgranules may be prepared in a taste-masked form in order to overcome the unpleasant taste of an API.
Granules and microgranules can be manufactured by fluid bed granulation or by wet granulation using a high shear mixer/granulator, followed by fluid bed drying. In the pharmaceutical industry, these operations are most commonly batch processes, with the “single-pot” process of fluid bed granulation holding an advantage.
Typically, high shear mixing/granulating produces somewhat denser (less porous) granules than fluid bed granulating (more porous), each having potential advantages depending on the target specification and application. The more porous granules resulting from a fluid bed granulation process may, for example, be an advantage for poorly soluble APIs. A fluid bed processor can also be used for the application of taste masking or other functional coatings, which may be applied to the granules and microgranules immediately after the granulation step.
Aqueous based and organic solvent based granulation solutions or suspensions can be processed, in addition to “hot melt” preparations of lipids and waxes. In addition to batch process granulation and microgranulation, Glatt Pharmaceutical Services also offers continuous granulation process technologies to develop and produce pharmaceutical granules.
Pellets
The development and manufacture of pellets and micropellets are among the primary core competencies of Glatt Pharmaceutical Services. In multi-particulate systems the dosage of a drug substance is, in contrast to single-unit forms like tablets, distributed among a plurality of sub-units, consisting of many spherical pellets or micropellets with a diameter typically in the range of 100 – 2000 µm.
Although their design and manufacture is more complex in comparison to classic single-unit dosage forms, multi-particulate dosage forms offer many interesting options and advantages to accomplish unique product characteristics, and in particular specific drug release patterns. With multi-particulate drugs an optimized pharmacokinetic behavior can enable improved patient compliance.
Micropellets are preferably used when taste masking of APIs must be provided (e.g. for ODTs, oral liquids, sachets, stick packs, dry suspensions). Taste masked micropellets are an interesting preparation in particular for pediatric, geriatric and veterinary drug products. Pellets and micropellets can be produced with numerous Glatt process technologies:
• Glatt fluid bed Wurster HS™ technology > drug layering + coating
• Glatt fluid bed CPS™ technology > direct pelletization dry powder drug layering
• Glatt fluid bed MicroPx™ technology > micropelletization
• Glatt fluid bed ProCell™ technology > granulation +(micro) pelletization
Wurster HS technology = Wurster High Speed technology
With these technologies available to our scientists, various drug layering liquids and coating liquids like solutions, suspensions, emulsions, micro-emulsions as well as hot melts can be applied. Furthermore, aqueous based and organic solvent based formulations are successfully processed.
Tablets
Tablets and minitablets
Tablets are the most widely used oral solid dosage form. In most cases, the API(s) is granulated before compression into tablets. In some cases, direct tabletting of the powder components is an option. A broad spectrum of formulation options is available with the basic monolithic tablet principle:
immediate release tablets
ODTs / orally disintegrated tablets
dispersible tablets
modified release tablets, achievable with coated tablets, matrix tablets, erodible tablets, etc.
Minitablets usually having a diameter of < 3 mm can be filled into capsules. Minitablets < 2 mm are applied for sachets and stick packs as well. Typically a modified drug release is achieved with film coated minitablets or with matrix minitablets. Taste masking materials are applied on minitablets when appropriate Film coating of tablets is a standard technology in pharmaceutical manufacturing. Different objectives are served when film coating is applied on tablets and minitablets: patient compliance / taste and smell masking, swallowability protection of API(s) against chemical degradation by light, oxygen, humidity improvement of physical stability of tablets protection of stomach against irritations by API(s) modification of drug release
Films can be applied from water based and organic solvent based liquids.
Tablet coating in perforated pan coaters is a standard technology today. In the Glatt Pharmaceutical Services Centers both aqueous and organic solvent based formulations are processed.
In special cases, film coating is applied using the fluid bed Wurster technology. Top coat drug layers and critical functional coatings can be applied on the tablet cores with highest precision.
MUPS
Multiple Unit Pellet Systems (MUPS) tablets are widely used in solid dosage form design. MUPS is considered to provide pharmacokinetic advantages compared to monolithic dosage forms. Typically, modified release pellets are contained in MUPS tablets.
Different dosage strengths exhibiting similar drug release characteristics can be achieved from one blend by varying the tablet mass and form only.
Combination of drug substances and release profiles can be provided by formulating the MUPS tablets with different pellet qualities or combining pellets with APIs in powder or granulated form.
Dispersible and ODTs
Dispersible and Orally Disintegrating Tablets (ODTs) allow improved patient compliance, in particular with paediatric, geriatric, and institutionalized patients.
Dispersible tablets are typically dispersed in water or another liquid before they are administered to the patient. This drug product is for patients having difficulties in swallowing solid dosage forms like tablets or capsules.
ODTs can be taken without water – a benefit for “dry” situations where water or other liquid drinks are not available.
A pleasant taste is achievable with appropriate taste-masking and flavoring, which is most often a mandatory requirement for such drug products.
Due to our extensive expertise in taste-masking, Glatt Pharmaceutical Services provide variable formulation concepts to achieve rapidly or fast disintegrating tablet formulations with excellent organoleptic properties.
The API(s) may be presented in the form of taste-masked API, micropellets or microgranules.
The micropellet dosage form concept easily allows the combination of the taste masking approach with a modified drug release approach. Therefore, dispersible tablets and ODT formulations can be applied for both immediate release and for modified release products
Capsules
Capsules are widely used as a highly flexible drug product vehicle. Capsules can be filled with powders, granules, pellets, tablets, minitablets, etc., including any combination thereof. Capsules are frequently used for blinded studies in the clinical development of drug products.
Capsules are mostly applied as oral dosage form products.
Capsules for inhalation are filled with micro-powders and applied with special inhalers. Since the API load per capsule is usually extremely low, a robust online weight control process system must be applied in order to guarantee the target drug load and content uniformity.
Fixed dose combinations
Fixed dose combination drug products contain more than one API in a fixed dose, allowing the patient to reduce the number of drug products to be taken. Improved patient compliance is the fundamental purpose of the fixed dose combination concept.
Different APIs (e.g. in the form of granules, pellets, micropellets) can be processed into tablets, capsules, stick packs, sachets, etc.
Pellets or micropellets with different release profiles are ideal basic formulation components for fixed dose combinations with defined drug release targets. They can be combined accordingly in order to provide an optimal drug release profile for the APIs included. Immediate release compounds can be comingled with modified release, gastro-resistant or pulsatile release components