University of Sulaimani School of Pharmacy Dept. of Pharmaceutics Third level - Second semester

University of Sulaimani School of Pharmacy Dept. of Pharmaceutics Third level - Second semester 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 1

Outlines Why rectal or vaginal route? Suppository Types of suppository base Glyceride-type fatty bases Water-soluble bases. Manufacturing Vaginal drug delivery 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 2

Why rectal or vaginal route? The patient is not able to make use of the oral route (unconscious, nausea). The drug under is not well suited for oral administration (acid sensitive, first pass effect) Where localized treatment of either the rectum or vagina is required. Drawback These routes are generally disliked by patients 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 3

Rectal drug delivery Local action: This is desired or the local treatment of pain and itching, mostly due to the occurrence of hemorrhoids (painful, swollen veins in the lower part of the rectum and anus). Antiseptics, local anesthetics, vasoconstrictors, anti-inflammatory and laxatives. Systemic action: Anti-asthmatic, anti-inflammatory and analgesic drugs Diagnostic purpose 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 4

Absorption of drugs from rectum Rectum is part of the colon, forming the final 15 20 cm of the GIT. The total volume of mucus is approx. 3 ml. ph is about 7.5 The lower and middle rectal (inferior and middle hemorrhoidal) veins drain into the interior vena cava the heart and general circulation. The upper rectal (superior hemorrhoidal) vein drains into the portal vein the liver the heart. Bioavailability will be low for certain drugs. 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 5

Suppositories Suppositories are the primary, dosage form used for the administration of drugs via the rectal route. They are single-dose preparations with a shape, volume and consistency appropriate for rectal administration. Others that should be inserted into body orifices like urethra is called bougies Rectal suppositories are usually about 1 4 g Cylindrical bullet shape. They contain one or more active substances dispersed or dissolved in a suit able base that may be soluble or dispersible in water or may melt at body temperature. 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 7

Suppository cont. Depending on the character of its vehicle, a suppository will either dissolve in the rectal fluid or melt on the mucous layer. Dissolution of the complete vehicle will be difficult and requires extra water. Unpleasant sensation for the patient Absorption of drug from the rectum is primarily by passive diffusion The rate and extent of drug absorption is lower than the oral route 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 8

Suppository base An ideal suppository vehicle or base should remain solid at room temperature and melt, dissolve or disperse at body temperature. It should be non-irritating, physically and chemically stable, and pharmacologically inert. It should be convenient to handle It should contract slightly on cooling to release itself from the mold with requiring mold lubricants Less leakage 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 10

Fatty base They are fully or semi-synthetic. Theobroma oil (also known as cocoa butter) a very commonly used base It melts at 30 C to 36 C It is no longer used because of its many disadvantages in practice, such: Its polymorphic behavior Insufficient contraction during cooling, Low softening point, Poor water absorptive power Expensive. 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 11

Fatty base cont. Commercial examples include: Cotmar, Fattibase, Suppocire and Witepsol. These are mixtures of natural or synthetic vegetable oils and fatty alcohol. High hydroxyl number Less hydrophobic High hydroxyl number high melting point easier manufacturing 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 12

Water-soluble base Hydrophilic water-soluble (or miscible) vehicles are much less frequently used. A. Glycerinated gelatin is a mixture of glycerol, gelatin and water. The mixture forms a translucent, gelatinous mixture, dispersible in the rectum. A higher proportion of gelatin in the mixture makes it more rigid and longer acting. They are mostly used for laxative purposes They are hygroscopic and require well-closed containers 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 13

Water-soluble base cont. B. Polyethylene glycols (macrogol): They consist of mixtures of polyethylene glycols of different molecular weight. Their melting point is higher than body temperature e.g. PEG 8000 (60 C to 63 C). PEGs are miscible with water and release the drug by diffusion. They are hygroscopic uncomfortable sensation of the patient. Incorporation of 20% of water and moistening before insersion. Poloxamers (Pluronics) are water-soluble, copolymers with a wide range of uses 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 14

Drug release Suppository either dissolve or melt in the rectum. If the release from the dosage form is considered as the rate-limiting step. The tendency to remain in the base should be lowered as much as possible Solubility in Fat Low High Low water High Low Low Choice of the vehicle Fatty base Aqueous base Not determined 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 15

Manufacturing Manufacturing the suppositories and pessaries are similar in both cases and involves: Melting of the vehicle Mixing the drug and the molten vehicle Dispensing the liquid into a shape former (molding) Cooling to solidify Packing in the final container. 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 17

Manufacturing cont. 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 18

Manufacturing cont. Depending on the formulation, suppository molds may require lubrication before the melt is poured to facilitate clean and easy removal of the molded suppositories Lubrication is not necessary when the base is cocoa butter or polyethylene glycol Lubrication is usually necessary with glycerinated gelatin 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 19

Outlines Why rectal or vaginal route? Suppository Manufacturing Vaginal drug delivery Pessaries Vaginal tablets Vaginal films Vaginal rings 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 20

Vaginal drug delivery Vaginal delivery is used for both local and systemic effects. Local effect Anti-infectives, like clotrimazole, miconazole, clindamycin. Contraceptive (spermicide) like nonoxynol-9 Hygiene and lubrication Drugs administered for local action in the cervico-vaginal area are not required to be absorbed. Systemic effect Drugs given by intravaginal route have a higher bioavailability compared to the oral route. E.g. oestrogens, progesterone and prostaglandin analogues 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 21

Vaginal drug delivery cont. Drugs designed for systemic action are absorbed by passive transport. Vaginal dosage forms include pessaries, liquids (vaginal solutions, emulsions, suspensions), semi-solids (creams, gels, ointments), solids (vaginal tablets, films, capsules and rings), spray and foams. Semi-solid formulations can serve dual purposes of providing medication as well as lubrication. 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 22

Pessaries Pessaries are solid, single-dose preparations or vaginal insertion. Pessaries can be prepared in various shapes, usually ovoid Most often prepared with glycerol-gelatin bases Polyethylene glycols are less common, since they are said to promote irritation. 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 23

Vaginal tablet Vaginal tablets are solid, single-dose preparations. Vaginal tablets can be prepared in various shapes, ovoid being the most popular Excipients are used to improve the disintegration of vaginal tablets, e.g. a bicarbonate together with an organic acid, which results in CO 2 release. A good filler for vaginal tablets is lactose 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 24

Vaginal films Vaginal films are thin layers of a polymeric material, which are designed to dissolve in the vaginal fluids and release the drug. Vaginal contraceptive film (VCF), containing nonoxynol-9 Itshould be inserted one an hour before sex Vagina should not be washed for at least 6 hour after sex. Both vaginal tablets and films can be designed to include bioadhesive polymers such as Carbopol and xanthan gum. 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 25

Vaginal rings Vaginal rings offer the flexibility of controlled release of the drug over a prolonged period of time. An example of vaginal ring is NuvaRing, containing estrogen and progestin, used as a contraceptive. It should left in the vagina for three weeks Acts for one month. 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 26

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