Semisolid dosage form

1. Semisolid dosage form Murat Kizaibek

2. Ointments • Ophthalmic ointments • Suppository

3. Concept Ointment base Adjuvants Preparation of ointments Quality control of ointments ointments

4. Definition: semisolid preparations intended for external application are termed ointments. Ingredient: drug substance +bases+ adjuvants Concept

5. Classification • According to the dispersion system: (1) solutions type (2) suspension type (3) emulsions type (1) oleaginous dosage form (2) emulsions dosage form (3) pastes dosage form (4) collodions dosage form (5) ophthalmic dosage form • According to the bases:

6. Quality requirement • the product is required smooth and uniform with certain stickiness to skin • the drug in bases even distributed • stability of the ointment • Skin infection preparations are designed to be sterile

7. Ointment bases are classified into four general groups: (1) Hydrocarbon bases (2) Absorption bases (3) Water-Removable Bases (4) Water-Soluble Bases Ointment bases

8. (1) hydrocarbon bases • Hydrocarbon bases (oleaginous bases) are water-free, and aqueous preparations may be incorporated into them only in small amounts and then with difficulty. • Hydrocarbon bases are retained on the skin for prolonged periods, do not permit the escape of moisture from the skin to the atmosphere, and are difficult to wash off. • As such they act as occlusive dressings. They do not "dry out" or change noticeably upon aging.

9. Petrolatum • a mixture of semisolid hydrocarbons obtained from petroleum • an unctuous mass, varying in color from yellow to white • It may be used alone or in combination with other agents as an ointment base • Commercial product is Vaseline

10. Paraffin • A purified mixture of solid hydrocarbons obtained from petroleum. • A colorless or white, more or less translucent mass that may be used to harden or stiffen oleaginous semisolid ointment bases.

11. Liquid paraffin a colorless, odorless oily liquid consisting of a mixture of hydrocarbons obtained from petroleum has the same character with paraffin be used in combination with paraffin to adjust viscosity

12. Hydrophilic Petrolatum • is composed of cholesterol, stearyl alcohol, white wax, and white petrolatum • has the ability to absorb water, with the formation of a water-in-oil emulsion. • Aquaphor is a highly refined variation of Hydrophilic Petrolatum and because it can absorb up to 3 times its weight in water, it has proven useful to incorporate extemporaneously a water-soluble drug into an oleaginous base.

13. Anhydrous Lanolin (refined wool fat) • may contain no more than 0.25% of water. • insoluble in water, but mixes without separation with about twice its weight of water • The incorporation of water results in the formation of a water-in-oil emulsion.

14. a semisolid, fatlike substance obtained from the wool of sheep. a water-in-oil emulsion that contains between 25 and 30% water. Additional water may be incorporated into lanolin by mixing. Lanolin (hydrous Wool Fat )

15. Beeswax and spermaceti • They are weak sufactants (W/O) and used as stabilization agents in O/W emulsive ointment.

16. a mixture of liquid hydrocarbons. It is useful as a levigating substance to wet and to incorporate solid substances into the preparation of ointments that consist of oleaginous bases as their vehicle. Mineral Oil

17. (2) Absorption bases • Absorption bases may be of two types: • those that permit the incorporation of aqueous solutions, resulting in the formation of water-in-oil emulsions (e.g. Hydrophilic Petrolatum and Anhydrous lanolin)and those that are already water-in-oil emulsions (emulsion bases) that permit the incorporation of small, additional quantities of aqueous solutions (e.g. lanolin and Cold Cream).

18. These bases are useful as emollients although they do not provide the degree of occlusion afforded by the oleaginous bases. • Absorption bases are not easily removed from the skin with water washing. • They are also useful pharmaceutically to incorporate aqueous solutions of drugs, e g., sodium sulfacetamide, into oleaginous bases.

19. (3)Water-Removable Bases • oil-in-water emulsions that are capable of being washed from skin or clothing with water. For this reason, they are frequently referred to as "water-washable" ointment bases • may be diluted with water or with aqueous solutions. • have the ability to absorb serous discharges in dermatologic conditions. • Certain medicinal agents may be better absorbed by the skin when present in a base of this type than in other types of bases.

20. Emulsifying agents • sodium lauryl sulfate :O/W emulsion • stearyl alcohol and cetyl alcohol representing the oleaginous phase of the W/O emulsion to improve the stabilization and viscosity. • sodium stearate and calcium stearate. • Glyceryl monostearate: weak W/O emulsifying agents and used as stabilization agents and emollient in the O/W emulsion.

21. Spans: W/O emulsifying agents Tweens: O /W emulsifying agents Peregal O and emulsive OP: O/W

22. Stearic acid, beewax and paraffin are the main oleaginous bases. propylene glycol and water representing the aqueous phase Methylparaben and propylparaben are used to preserve the ointment against microbial growth

23. (4) Water-Soluble Bases • contain only water-soluble components. • are water washable • Because they soften greatly with the addition of water, aqueous solutions are not effectively incorporated into these bases. Rather, they are better used for the incorporation of nonaqueous or solid substances.

24. Polyethylene Glycol Ointment • Polyethylene glycols are polymers of ethylene oxide and water • The chain length may be varied to achieve polymers having desired viscosity and physical (liquid, semisolid, or solid) form. • The general formula for this base calls for the combining of polyethylene glycol 3350(a solid) and polyethylene glycol 400 (a liquid) to prepare base.

25. Antioxidants Antimicrobial preservatives Adjuvants

26. Antioxidants

27. Antimicrobial preservatives • frequently require the addition of chemical antimicrobial preservatives to the formulation to inhibit the growth of contaminating microorganisms • These preservatives include: para-hydroxybenzoates (parabens), phenols, benzoic acid, sorbic acid, quaternary ammonium salts and other compounds.

28. Selection of the Appropriate Base The selection of the base to use in the formulation of an ointment depends upon the careful assessment of a number of factors, including : (a) the desired release rate of the particular drug substance from the ointment base (b) the desirability for enhancement by the base of the percutaneous absorption of the drug

29. (c) the advisability of occlusion of moisture from the skin by the base (d) the short-term and long-term stability of the drug in the ointment base (e) the influence, if any, of the drug on the consistency or other features of the ointment base. (f) patient factors also play an important role in a base's selection

30. Both on a large and a small scale, ointments are prepared by three general methods: (1) incorporation method (2) fusion method (3) emulsification method The method for a particular preparation depends primarily upon the nature of the ingredients Preparation of Ointments

31. (1) incorporation • the components of the ointment are mixed together by various means until a uniform preparation has been attained. • On a small scale, the pharmacist may mix the components of an ointment in a mortar with a pestle, or a spatula and an ointment slab (a large glass or porcelain plate) may be used to rub the ingredients together.

32. By the fusion method, all or some of the components of an ointment are combined by being melted together and cooled with constant stirring until congealed. Those components not melted are generally added to the congealing mixture as it is being cooled and stirred. Naturally, heat-labile substances and any volatile components are added last when the temperature of the mixture is low enough not to cause decomposition of volatilization of the components. (2) fusion

33. In the preparation of ointments having an emulsion type of formula, the general method of manufacture involves a melting process as well as an emulsification process. (3) emulsification

34. the water-immiscible components such as the oil and waxes are melted together in a steam bath to about 70 to 75°C Meantime, an aqueous solution of all of the heat-stable, water-soluble components is being prepared in the amount of purified water specified in the formula and heated to the same temperature as the oleaginous components.

35. Then the aqueous solution is slowly added, with constant stirring (usually with a mechanical stirrer), to the melted oleaginous mixture, the temperature is maintained for 5 to 10 minutes to prevent crystallization of waxes the mixture is slowly cooled with the stirring continued until the mixture is congealed.

36. Notice: • If the aqueous solution were not the same temperature as the oleaginous melt, there would be solidification of some of the waxes upon the addition of the colder aqueous solution to the melted mixture. Emulsification ointments

37. Concept semisolid preparations intended for application to the eye are specially prepared and are termed ophthalmic ointments. Ⅱophthalmic ointments

38. The methods of preparation just like ointments,but under the aseptic condition for prevent eye infection. Preparation of ophthalmic ointments

39. The bases • must be non-irritating to the eye and must permit the diffusion of the medicinal substance throughout the secretions bathing the eye. • Ointment bases utilized for ophthalmics have a melting or softening point close to body temperature. • In most instances, mixtures of petrolatum and liquid petrolatum (mineral oil) are utilized as the ointment base. • Sometimes a water-miscible agent as lanolin is added. This permits water and water-insoluble drugs to be retained within the delivery system.

40. The advantage and disadvantage • The primary advantage of an ophthalmic ointment over an ophthalmic solution is the increased ocular contact time of the drug. • One disadvantage to ophthalmic ointment use is the blurred vision which occurs as the ointment base melts and is spread across the lens.

41. Suppositories

42. Suppositories are semisolid dosage forms intended for insertion into body orifices where they melt, soften, or dissolve and exert localized or systemic effects. 1.Definition

43. Suppositories are commonly employed rectally, vaginally and occasionally urethrally. They have various shapes and weights depending upon the density of the base and the medicaments present in it, and the individual manufacturer's product. 2. Body orifices for using

44. Vaginalusing Rectal using Shape of suppositories

45. Rectal suppositories are most frequently employed to relieve constipation or the pain, irritation, itching, and inflammation associated with hemorrhoids or other anorectal conditions. Vaginal suppositories or inserts are employed mainly as contraceptives, antiseptics in feminine hygiene, and as specific agents to combat an invading pathogen. Urethral suppositories may be used as antibacterial and as a local anesthetic preparative to urethral examination. 3.character of action 1)Local Action

46. (a) for the relief of nausea and vomiting and as a tranquilizer (b) for narcotic analgesia (c) for the relief of migraine syndrome (d) anti-inflammatory analgesic and antipyretic. 2)Systemic Action administered rectally in the form of suppositories for systemic effects include:

47. (a) drugs destroyed or inactivated by the pH or enzymatic activity of the stomach or intestines need not be exposed to these destructive environments; (b) drugs irritating to the stomach may be given without causing such irritation; (c) drugs destroyed by portal circulation may bypass the liver after rectal absorption (drugs enter the portal circulation after oral administration and absorption); 3) advantages over oral therapy(rectal route for achieving systemic effects )

48. (d) the route is convenient for administration of drugs to adult or pediatric patients who may be unable or unwilling to swallow medication; (e) it is an effective route in the treatment of patients with vomiting episodes.

49. the medicaments and base mixed uniformly with certain hardness under condition of shipment and storage capable of being easily inserted into the intended body orifice without causing undue distension. once inserted, the base melts, softens, or dissolves, distributing the medicaments it carries to the tissues of the region. It must be retained for the appropriate period of time for local effects or quickly absorbed for systemic effects . 4.Quality control of suppository The shape and size of a suppository must be such that

50. contains drug,base and other adjuvant ,which the affecting factors for preparation are the physicochemical nature of the drug, the nature of the suppository vehicle and its capacity to release the drug and clinical desired effects from administration 。 Drug properties as the relative solubility of the drug in lipid and in water , the particle size of a dispersed drug. Ⅱ Ingredients of suppositories