Whatever the oral product, Upperton's expertise helps you develop it
Oral drug delivery remains the most preferred and convenient route for drug administration, due to high patient compliance, cost-effectiveness and ease of production. Tablets and capsules are the most frequent dry powder dosage form for the oral route. However, other dosage forms such as sachets (bulk powders) or granules / powder for reconstitution are also used.
Spray drying is the most flexible, cost-effective technique for producing dry powder formulations and providing an enabling formulation strategy for the delivery of challenging molecules by the oral route.
One of the most important aspects in the development of oral dosage forms is formulation development. It is at this stage that the bulk powder properties required for successful processing into a dosage form will be determined.
Avoiding drug release in the stomach may be an essential aspect in developing a successful oral dosage form; this may be true for both small molecules and biotherapeutics. In order to avoid destruction from an acidic environment, targeting to specific regions of the digestive system are necessary in order to optimise therapeutic delivery. This can be readily achieved using commercial tablet coatings or capsules.
Excipients such as disintegrants, lubricants, flow aids & bulking agent / fillers are often added to formulations. This can be to improve powder properties during processing (a powder blend with good content uniformity and flow is important for capsule filling / tabletting) as well as the eventual performance of the final dosage form.
Developing a solid oral dosage form can present many challenges to the formulation scientist in the early stages of development. Upperton offers a rapid screening protocol UpperSolv™ Which can be used to generate comparative data (including a PK assessment) with minimal API in a cost-effective and time saving study.
Tablet dosage forms allow a range of delivery mechanisms to be achieved to meet patient needs.
Tablet manufacture is a well-defined process, with a number of key steps.
- Granulation – Densification of powders to increase bulk density and improve flow can be achieved using granulation (wet granulation and dry granulation using roller compaction). This is commonly used for spray dried powders which often have low bulk density.
- Compression – Tablet compression can be undertaken using either a single station tablet press or high speed rotary multi-station tablet machine with dedusting and metal detection. The scale of manufacture will define the importance of powder properties, small-scale tablet manufacture can be used to characterise initial formulations by properties such as compressibility & manufacturability, disintegration and dissolution. Thorough characterisation of the product at this stage is beneficial before ascending to larger scale manufacture.
- Coating – Film coating of tablets is common during commercial manufacturing, with functionalities including taste masking, elegance/colour matching and improved stability. A range of functional coatings are available to provide sustained release over time or delayed release (enteric pH protection).
Manufacturing equipment includes: Futorque Tablet Press, O’Hara Lab Coater and Vector Roller Compactor.
Filling spray dried powders and other APIs into hard shell HPMC or gelatin capsules, enables projects to move more quickly into first in human (FIH) or proof of concept (POC) studies. Capsules can be filled manually, which avoids extensive formulation development before clinical data can be achieved.
As the trial progresses through the clinical stages; scale up of batch size is managed through automation, into semi-automated capsules fillers (Profill range) and then onto fully automated capsule filling machines capable of producing several thousand capsules per hour.
When developing the approach to capsule filling, consideration should be given to the target formulation, powder properties and the dose required, as these will dictate the method of manufacture:
- Simple flood fill
- Bulking agent required to enhance powder handing/filling operations
- Precision fill
Manufacturing equipment includes: Torpac Capsule Fillers and Quantos Precision Filler.