Medicine Design & Manufacture: Solid Dosage Forms Notes

Topic Aim

  • Understand the development of solid dosage forms (SDFs) and important factors contributing to their design.

Solid Dosage Forms (SDFs)

  • Oral SDFs: Tablets, Capsules, Oromucosal preparations

  • Non-Oral SDFs: Rectal preparations, Vaginal preparations

Learning Outcomes

  1. Definition of ‘solid dosage forms’ and ‘oral solid dosage forms’.

  2. Definition and aspects of powders in solid dosage formation.

  3. Analyze powder size.

  4. Uses and methods of particle size reduction.

  5. Powder separation methods.

  6. Requirement and methods for powder mixing.

  7. Understand powder flow characteristics and their impact on SDF preparation.

  8. Identify additional components needed for oral solid dosage forms.

Oral Solid Dosage Forms (OSDFs)

  • Medicinal products delivered via the mouth to be absorbed through the gastrointestinal system.

  • Tablets: Solid preparations containing active ingredients, compressed or manufactured through extrusion, moulding, or freeze-drying. Swallowed whole, chewed, dissolved in water, or retained in the mouth for absorption.

  • Capsules: Solid preparations in hard or soft shells, containing active substances, filled and closed by various means. Shells dissolve in digestive fluids to release contents.

Powder Characteristics

  • Particle size, shape, density, and material strength influence medicine characteristics.

  • Factors Influencing Design of SDFs include:

    • Size classification:

      • Coarse: > 1000 µm

      • Intermediate: 100 µm < 1000 µm

      • Fine: 5 µm < 100 µm

      • Ultrafine: < 5 µm

    • Shapes affect flow properties: Spherical for good flow, Acicular for poor flow.

Particle Size Analysis Methods

  • Light-based methods:

    • Microscopy: Standard and advanced SEM/TEM for particle examination.

    • Laser light diffraction: For size range 0.5 – 3500 µm.

    • Photon correlation spectroscopy: For size range 0.3 nm – 10 µm.

  • Sieving methods: Traditional and air jet for size separation, important in granulation processes.

  • Other methods: Time of flight measurements, electrical stream sensing zone method, sedimentation based on physical principles.

Particle Size Distribution Results

  • Results can be displayed as histograms/size frequency curves, indicating size distribution of powders pre-and post-reduction.

  • Cumulative size distribution can represent oversize or undersize metrics, useful for quality control.

Mixing and Particle Characteristics

  • Mixing processes aim to create uniform compositions, with terms:

    • Mixing = blending, Segregation = the separation of mixed particles.

    • Types of mixtures: Positive (well mixed), Negative (segregate), Neutral (energy needed for movement).

  • Scale of scrutiny (S o S) guides sample size needed for evaluation of mixing adequacy.

Particle Size Reduction (Comminution)

  • Goals: Achieve desired particle size for improved processing and dissolution rates. Relevant equations:

    • Noyes-Whitney equation: dC / dt = DA (Cs – C) / h
      Where D = diffusion coefficient, A = surface area, Cs = saturation concentration, C = concentration in solution, h = diffusion layer thickness.

  • Issues in reduction could include aggregation, contamination, and changes in product characteristics.

Excipients in SDFs

  • Non-active compounds that serve to bulk out the API, assist in production and improve bioavailability.

  • Common examples include:

    • Diluents: Lactose, mannitol, microcrystalline cellulose.

    • Binders: Acacia mucilage, cellulose derivatives, PVP.

    • Disintegrants: Facilitate breakdown of tablets; e.g., sodium starch glycolate, MCC.

    • Glidants and lubricants: Improve flow properties and prevent adherence.

    • Flavours and sweeteners: Enhance palatability for patient compliance.

Important Notes on Production

  • Understand mechanisms of coating and solvent interactions often used to enhance bioavailability and improve product stability.

  • Recognize that directed study content is examinable, emphasizing the importance of thorough preparation.

Questions

  • Students are encouraged to complete the directed study provided on the Moodle for assessment preparation.