Suppositories controlled release

Cosmetics and Pharmaceuticals. The main use of hexadecanol (cetyl alcohol) is in cosmetics (qv) and pharmaceuticals (qv), where it and octadecanol (stearyl alcohol) are used extensively as emoUient additives and as bases for creams, Hpsticks, ointments, and suppositories. Octadecenol (oleyl alcohol) is also widely used (47), as are the nonlinear alcohols. The compatibiHty of heavy cut alcohols and other cosmetic materials or active dmg agents, their mildness, skin feel, and low toxicity have made them the preferred materials for these appHcations. Higher alcohols and their derivatives are used in conditioning shampoos, in other personal care products, and in ingested materials such as vitamins (qv) and sustained release tablets (see Controlled RELEASE technology). 

Vaginal 20 mg suppositories, 0.5 mg gelVaginal 20 mg suppositories, 0.5 mg gel, 10 mg controlled-release system Epoprostenol [prostacyclin] (Flolan)... 

Oral Asacol 400 mg delayed-release tablets Pentasa 250 mg controlled-release capsules Rectal Rowasa 4 g/60 mL suspension Canasa 500, 1000 mg suppositories Methylprednisolone (Medrol Enpack)... 

Takatori T, Yamamoto K, Yamaguchi T, Higaki K, Kimura T. Design of controlled -release morphine suppositories containing polyglycerol ester of fatty acid. Biol Pharm Bull 2005 28(8) 1480-1484. 

The rectal milieu is quite constant as its pH is about 7.5, and the temperature is usually 37°C. It is normally empty and the pressure varies between 0 and 50 cm. This makes this route suitable for the (controlled) delivery of drugs by applying adequate (controlled release) dosage forms such as osmotic pumps and hydrogels, since the classical suppositories are, in general, not the most suitable dosage form to achieve a reproducible rate and extent of drug absorption. 

Miyake, M., et al. 2004. Development of suppository formulation safely improving rectal absorption of rebamipide, a poorly absorbable drug, by utilizing sodium laurate and taurine. J Control Release 99 63. 

Dissolution rate tests for tablets, capsules, suspensions, suppositories, or other dosage forms. Controlled-release dosage forms or drug delivery systems also should be monitored by appropriate testing methodology. 

Aspirin is commercially available in numerous formulations (Table 7-1). It is compounded as a tablet, an enteric-coated tablet, a controlled-release tablet, and as a suppository. Enteric-coated aspirin, which decreases GI tract irritation, is recommended for chronic use but is rarely required for the treatment of acute ocular pain, which usually resolves over several days. Likewise, controlled-release aspirin, because of its relatively long onset of action, is not recommended for treatment of acute ocular pain. 

Yahagi, R. Onishih, H. Machida, Y. Preparation and evaluation of double-phased mucoadhesive suppositories of lidocaine utilizing carbopol and white beeswax. J. Controlled Release 1999, 61, 1-8. 

Accepted in Europe as a food additive in certain applications. Included in the FDA Inactive Ingredients Guide (oral capsules, tablets and suspensions, topical suspensions, controlled release transdermal films and vaginal suppositories). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients. 

Glyceryl monostearate is a lubricant for tablet manufacturing and may be used to form sustained-release matrices for solid dosage forms.Sustained-release applications include the formulation of pellets for tablets or suppositories and the preparation of a veterinary bolus. Glyceryl monostearate has also been used as a matrix ingredient for a biodegradable, implantable, controlled-release dosage form. ... 

Stearyl alcohol is used in cosmetics and topical pharmaceutical creams and ointments as a stiffening agent. By increasing the viscosity of an emulsion, stearyl alcohol increases its stability. Stearyl alcohol also has some emollient and weak emulsifying properties and is used to increase the water-holding capacity of ointments, e.g. petrolatum. In addition, stearyl alcohol has been used in controlled-release tablets, " suppositories, and microspheres. It has also been investigated for use as a transdermal penetration enhancer. ... 

Mesalamine (5-aminosalicylic acid asacol, others) is a salicylate that is used for its local effects in the treatment of inflammatory bowel disease (see Chapter 38). It currently is available as a suppository and rectal suspension enema (rowasa) for treatment of mild-to-moderate proctosigmoiditis Cl rectal suppository (canasa, others) for the treatment of distal ulcerative colitis, proctosigmoiditis, or proctitis. Oral formulations and controlled-release capsule that deliver drug to the lower intestine are efficacious in treatment of inflammatory bowel disease, in particular ulcerative colitis. Sulfasalazine (salicylazosulfapyridine azulfidine) contains mesalamine linked covalently to sulfapyridine (see Chapter 38) it is absorbed poorly after oral administration, but it is cleaved to its active components by bacteria in the colon. The drug is of benefit in the treatment of inflammatory bowel disease, principally because of the local actions of mesalamine. 

Contemporary research focuses on the development of dosage forms with a better and faster release of the active substance and on dosage forms with a delayed or controlled release. The addition of surfactants to the suppository often enhances the rate and extent of release and even the absorption of an active substance, but there are many exceptions. For a delayed or controlled release an increased viscosity of the suppository mass appears to be relevant. Most research has not yet yielded a licensed medicine. 

Controlled release by increasing the viscosity of the suppository base has been studied with morphine. 

Metoclopramide hydrochloride controlled release suppositories were prepared by mixing Witepsol W35 with 30 % lecithin [13]. The metoclopramide is incorporated in this base in a (solid) reversed micellar solution. The diffusion rate of the active substance from the melted suppository in contact with the aqueous rectum fluid was very low. Compared to licensed normal metoclopramide suppositories a five times longer mean residence time was found in vivo for the lecithin suppositories. 

Moolenaar F, Meijler WJ, Frijlink HW et al (2000) Clinical efficacy, safety and pharmacokinetics of a newly developed controlled release morphine sulphate suppository in patients with cancer pain. Eur J Clin Pharmacol 56 219-223... 

Schneeweis A, Miiller-Goymann CC (2000) Controlled release of solid-reversed-micellar-solution (SRMS) suppositories containing metoclopramide-HCl. Int J Pharm 196 193-196... 

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