Chapter 6 Solid preparation

1. Chapter 6 Solid preparation Dr. Lei Luo 15730075066@sina.cn

2. Requirements • To understand the definition, characteristics and preparation methods of powders, granules, capsules, drops and pills. (2) Master the preparation process, influencing factors and quality control of granules and capsules; (3) Master the prescription design of tablets, the classification and application of excipients, the process and equipment of tableting; (4) Master the quality evaluation of tablets.

3. 5 1 2 3 4 Powders Granules Capsules Tablets Drops and films Contents

4. Solid preparation producing flow chart Powders Capsules Granules Tablets

5. 1. Powders 1.1 Definition Powdersare mixtures of dry, fine, divided drugs and/or chemicals that may be intended for internal (oral) or external (topical) use. • May be intended for internal use or external use, but most frequent use is external. • Use as a dosage form is limited, but use in preparation of other dosage forms is extensive.

6. Noyes-Whitneyequation Dissolution rate: dC/dt=KS (CS-C) K=D/Vδ K- dissolution rate constant S- surface area of undissolved solid D- diffusion constant of drugCS- solubility in dissolution medium δ- Thickness of boundary layer C-concentration in medium V- Volume of dissolution medium

7. 1.2 Administration routes • Oral: oral powders, effervescentpowders • Inhalation: dry-powder as pulmonary DDS • Nasal • Topical: large open wound • Ear powder • Preparing for further treatment: suspension, syrup, oral drops, injection

8. 1.3 Advantages and disadvantages a) Chemically stable and long shelf-life b) Convenient for patients c)Orally powders fast dissolution d)Topical powders large spread area

9. 1.3 Advantages and disadvantages a) Less convenient than tablets or capsules b)Hard to mask unpleasant taste c) Difficult to protect from atmospheric moisture or oxygen d)Not suitable for low dose (difficult measurement) e) Not suitable for drugs irritate or damage stomach

10. Divided Powders • Have generally fallen into disuse because of the ready availability of tablets and capsules. • Some commercial OTC products are packaged in similar unit-dose packets: –BC Headache Powders –Stanback Analgesic Powders

11. 1.4 Packing • The divided portions are each placed on a small piece of paper, which is then folded to enclose the medication (powder papers). Avoiding moisture or oxygen!

12. Notice for blending powders • Low dosage or toxic drug－Equivalent multiplied • Liquid or extract－Absorbent

13. 2. Granules 2.1 Definition Prepared by agglomerating of smaller particles of powder. • Generally irregular in shape, as opposed to spherical. • Often in 4 to 12 mesh size, depending on application –May be dispensed in bulk as a dosage form for oral administration, e.g. as antacid, dietary supplement etc. –Widely used as an intermediate for making compressed tablets or filling into capsules

14. Why granules? • Prevent powder segregation • Size enlarge --- better flowability • better compressibility than powders (binders) – advantage in making tablets or filling capsules (feeding of high-speed equipment) • Less surface area – More stable to atmospheric moisture/oxygen – Less likely to cake in the container than powders – Reduce toxic dust during handling

16. Granulators Fluid-Bed High shear granulator

17. Fluid Bed Granulation Requires proper balance of inlet air temperature and feed rate. –For a given feed rate: • Higher feed rates increases the ‘evaporative load’ and slows drying; tends to produce larger, denser and stronger granules • Lower feed rates tend to produce smaller, friable granules –For a given inlet temperature • Higher inlet air temperatures cause rapid evaporation of the binder solution and results in smaller, friable granules. • Lower inlet temperatures, drying is slower (particles stay wetter longer); produces larger, denser, stronger granules.

18. Wet granulation is not practical for drugs sensitive towater or heat…

19. Dry Granulation Roller Compaction –Powder blend force between rollers to form a cake (“ribbon”) –Cake milled to form granules Dry binders.i.e. Microcrystalline cellulose

20. Effervescent Granulated Salts“Effervescent Salts” Effervescent granules contain medicinal substance usually in combination with sodium bicarbonate, citric acid and tartaric acid. • Carbon dioxide forms with placed in water. • Carbonation helps mask the unpleasant taste of drugs. • Granular form (as opposed to power form)

21. Question Tartaric acid Citric acid Sodium bicarbonate NaHCO3

22. 3. Capsules 3.1 Definition Capsule is a shell or a container prepared from gelatin containing one or more medicinal and/or inert substances. • Hard Shell Capsules (Two pieces) • Soft Shell Capsules (One piece)

23. Why gelatin? Gelatin is prepared by the hydrolysis of collagen, from animal skins and bones. • Non-toxic and widely used • Readily soluble in biological environment • Decent film-forming material • Solutions of high polymer concentration (40% w/v) • Reversible change from a sol to a gel

24. Advantages （1）Odorless and tasteless （2）Stability (barrier to oxygen and moisture) （3）Easily swallow, improve bioavailability （4）Controlled drug release

25. Disadvantages （1）The drugs which are hygroscopic absorb water from the capsule shell making it brittle and hence are not suitable for filling into capsules. （2）The concentrated solutions which require previous dilution are unsuitable for capsules because if administered as such lead to irritation of stomach.

27. Preparation • Bosch GKF 1500 Dosing Disc Machine • 90,000/hr

28. Soft capsules • Similar to hard gelatin shell, except plasticizeris incorporated (sorbitol, propylene glycol, glycerin) • Usually filled with liquids or suspensions (dry solids are possible, including compressed tablets (“Geltabs”).

29. Formulation for soft capsules • Pure liquids, mixtures of miscible liquids, or solids dissolved or suspended in a liquid vehicle. • Vehicles Water immiscible non-volatile liquids • Vegetable oils • Mineral oil not recommended Water-miscible, non-volatile liquids • Low molecular weight PEG's • Nonionic surfactants such as polysorbate 80

30. Limitations of Liquid Contents • Water cannot exceed 5% of contents • pH must be between 2.5 and 7.5 • Low molecular weight water soluble and volatile compounds must be excluded • Aldehydes need excluded (Cause cross-linking) • Contents must flow under gravity at < 35

31. Rotary Die process

32. Quality consideration • Ingredient specifications • In-process testing • Finished product testing Self reading on P609 Aulton’s Pharm

33. Thank You