Developing Oral Dosage Forms for Clinical Trials

Producing a spray dried powder is rarely the end of developing oral dosage form pathway. Further processing is usually required in order to create a oral dosage form that can be administered in First-in-Human (FIH) or Proof of Concept (POC) clinical studies.

The selection of a dosage form will involve a number of factors, for example:

  • Pharmacokinetics
  • Bioavailability
  • Stability under ambient climatic conditions
  • Excipient compatibility
  • The determined route of administration and the ability to achieve patient compliance
8ml round Tablet Dosage Forms made in Upperton's Manufacturing Clean Suite for FIH studies

Tablets and capsules are the most common oral dosage form. However, other dosage forms such as sachets (bulk powders), vials (for reconstitution) and powders delivered via devices (inhalation and nasal) are also required on a regular basis.

Designing a Process for Tablet Manufacture

In general, processes for tablet manufacture require the following 3 step processes:

  • Granulation – Dry granulation (roller compaction, slugging) is the most common technique for spray dried powders. Alternatively, spray dried powders can be blended and subjected to direct compression.
  • Compression – Conventional rotary multi-station compressing machine with dedusting and metal detection. Flexibility in tablet size and shape can be managed using conventional and multi-tip tooling.
  • Coating – Utilisation of a film or sugar coating can be used for a variety of purposes including taste masking, improving stability and for targeted release in the digestive tract.

Designing a Process for Capsule Manufacture

Filling spray dried powders and other API’s into hard shell HPMC or gelatin capsules enables projects to move more quickly into FIH or POC studies.

In many cases, it is possible to fill capsules manually. 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. This will essentially dictate the method of manufacture, in particular;

  • Is a simple flood fill with the spray dried powder possible?
  • Is a bulking agent required to enhance powder handing/filling operations?
  • Is a Precision fill of the spray dried powder directly into the capsule more appropriate?

Drugs that have short half-lives or are rapidly metabolized often require dosing three or four times a day to maintain drug levels in the required therapeutic range. In such cases, sustained-release dosage forms can reduce the frequency of dosing.

The selection and use of specifically designed capsule coatings can create sustained-release products that can reduce the frequency of drug administration; improving compliance and the therapeutic effectiveness of the drug by maintaining a more constant drug plasma level than can be obtained using traditional dosage forms.

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