Oral dosage Forms
Whatever oral product, Upperton's expertise helps you develop it
Spray drying is the most flexible, cost effective technique for producing dry powder formulations for delivery by the oral route.
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 common 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.
Avoiding drug release in the stomach may be an essential aspect in developing a successful oral dosage form. This may be true for small molecules and biotherapeutics in order to avoid destruction in the acid environment of the stomach or for targeting to specific regions of the digestive system in order to optimise delivery into the body. This can be readily achieved using commercial tablet coatings or capsules.
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.
Excipients such as disintegrants, lubricants, flow aids & bulking agent/fillers are often added to powder formulations. This can be to improve powder properties during processing (a powder blend with good content uniformity and flow is important for capsule filling and tabletting) as well as the eventual performance of the final dosage form.
Filling spray dried powders and other APIs into hard shell HPMC or gelatin capsules enables projects to move more quickly into FIH or 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
Capsule formulations can be progressed to commercial manufacture, although it is often that a tablet will be preferred for the wider market. Although more development is required than for capsule manufacture, tablet dosage forms allow a greater range of modifications (such as shape, size, appearance), can accommodate higher dose drugs and provide longer shelf life.
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 dry granulation (roller compaction, slugging). This is commonly used for spray dried powders which often have low bulk density.
- Compression – Tablet compression can be undertaking using single station tablet presses to conventional rotary multi-station compressing machine with dedusting and metal detection. The scale of manufacture will define the importance of powder properties, and 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 beneficially before scaling up 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).