Suppository formulations

Suppositories are probably more difficult to study in vitro than many other dosage forms because it is not easy to simulate the conditions in the rectum. In one system, shown in Fig. 12.5, a suppository is placed in a pH 7.8 buffer in a dialysis bag. This bag is placed in a second dialysis bag filled with octanol, the whole is suspended in a flow system at 37°C, and the amount of drug released into the outer liquid is monitored. The results from this set-up must be interpreted with care as it is possible for substances that complex with the drug to reduce transport across the dialysis membrane - something which may or may not happen in the body. 

A variant on this arrangement was used to obtain the data shown in Fig. 12.6 illustrating the reduction in aminophylline release from Witepsol H15 bases on ageing of the product. 

2 fn vitro release from topical products and transdermal systems 

Hydrodynamic characfer-isfics of /he apparatus types of agitation intensity of agitation dispersion of particles Properties of Hie dissolution fluid pH 

Operating conditions agitation intensity volume of solvent exchange of solvent 

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Xue et al. [30] prepared a vaginal suppository formulation containing miconazole nitrate and determined its content by P-matrix ultraviolet spectrophotometry. The production of the suppository was finished with melting by the excipient of glyceryl esters fatty acid of artificial synthesis. Quantitative assay was conducted with a P-matrix ultraviolet spectrophotometer. The suppository was smooth and met the clinical requirement of vaginal disease treatment. The method of assay was accurate. 

Bisacodyl is available in tablet and suppository formulations for the treatment of acute and chronic constipation. It also is used in conjunction with PEG solutions for colonic cleansing prior to colonoscopy. It induces a bowel movement within 6-10 hours when given orally and 30-60 minutes when taken rectally. It has minimal systemic absorption and appears to be safe for acute and long-term use. Phenolphthalein, another agent in this class, was removed from the market owing to concerns about possible cardiac toxicity. 

Hosny, E.A., et al. 2003. Evaluation of efficiency of insulin suppository formulations containing sodium salicylate or sodium cholate in insulin dependent diabetic patients. Boll Chim Farm 142 361. 

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

A suppository formulation based on progesterone was proposed to prevent cystic hyperplasia of the endometrium and possible cancer formation during postmenopausal long-term estrogen therapy [31]. 

McEvoy, E., Donegan, S., Power, J., Altria, K.D. Optimisation and validation of a rapid and efficient microemulsion liquid chromatographic (MELC) method for the determination of paracetamol (acetaminophen) content in a suppository formulation. J. Pharm. Biomed. Anal. 44, 137-143 (2007)... 

The inclusion of a surfactant in the suppository formulation may enhance the rectal absorption of drugs. The effect has been attributed to the formation of mixed micelles. It has been suggested that the presence of the micelle facilitates the incorporation of the lipid component of the mixed micelle into the biological membrane. This lipid then enhances the fluidity and permeability of the membrane to the poorly absorbed drug. It appears that the colorectal mucous membrane is more sensitive to the effects of mixed micelles than the gastrointestinal membrane of the small intestine. 

Tribenoside, ethyl-3,5,6-tri-O-benzyl-D-glucofuranoside, is used as an anti-hemorrhoidal in oral and suppository formulations. 

In aerosols, other than those for inhalation, colloidal silicon dioxide is used to promote particulate suspension, eliminate hard settling, and minimize the clogging of spray nozzles. Colloidal silicon dioxide is also used as a tablet disintegrant and as an adsorbent dispersing agent for liquids in powders. Colloidal silicon dioxide is frequently added to suppository formulations containing lipophilic excipients to increase... 

Novak E, Osborne DW, Matheson LE, et al. Evaluation of cefmetazole rectal suppository formulation. Drug Dev Ind Pharm 1991 17(3) 373-389. 

Polyoxyethylene alkyl ethers have also been used in suppository formulations to increase the drug release from the suppository bases. ... 

Berko S, Regdon GJr, Eros I. Solutol and cremophor products as new additives in suppository formulation. Drug Dev Ind Pharm 2002 28 203-206. 

Studies have shown that yellow wax, when added to suppository formulations, increased the melting point of the preparation significantly and decreased the rate of release of the active substance. ... 

Apparatus for studying the many variables in suppository formulation has been designed to measure rates of release in vitro. Both a circulating dissolution apparams and a dialysis device utilising an aqueous and a nonaqueous phase have been described, and are discussed in section 12.3.1. 

N. M. Idkaidek, G. L. Amidon, D. E. Smith, N. M. Najib, and M. M. Hassan, Determination of the population pharmacokinetic parameters of sustained-release and enteric-coated oral formulations, and the suppository formulation of diclofenac sodium by simultaneous data fitting nsing NONMEM. Biopharm Drug Dispos 19 169-174 (1998). 

Several different suppository formulations were evaluated in monkeys to determine the formulation that maximized bioavailahility and reduced first-pass metabolism of THC by the fiver (Mattes et al. 1993, 1994) THC-hemisuccinate provided the highest bioavailahility of 13.5%. Brenneisen et al. evaluated plasma THC concentrations in two patients who were prescribed THC hemisuccinate suppositories or Marinol for spasticity (Brenneisen et al. 1996). THC did not accumulate in the blood following 10 to 15 mg daily doses. THC concentrations peaked within 1 to 8 h after oral administration and ranged between 2.1 and 16.9 ng/ml. Rectal administration of 2.5 to 5 mg THC produced maximum plasma concentrations of... 

Other applications of DSC and other TA techniques to the pharmaceutical industry include physico-chemical interactions (275), polymorphism in triglyceride suppository formulations (276) drug-excipient interactions (277), and many more. Reviews of the applications of DTA/DSC and different techniques to pharmaceuticals include those by Brennan (278), Daly (279), and others (280). 

Drug overdose A 20-year-old man with ulcerative proctitis took a rectal suppository formulation of mesalazine 7500 mg orally and 7000 mg of the same formulation rectally [99 ]. He developed a headache, dizziness, nausea, and pain in the rectum. Colonoscopy showed diffuse hjrperemia and edema extending from the anal channel to the proximal rectal mucosa and a 1.5-cm... 

Certain fat based suppositories formulations contain a lipophilic liquid, such as Miglyol 812 in zinc oxide suppositories (see Table 11.2). Such a liquid is very useful for trituration and cannot solidify in the meantime, as a molten suppository base often does. 

Liversidge, G. G., Nishihata, T., Engle, K. K., and Higuchi, T., 1985, Effect ofrectal suppository formulation on the release of insulin and on the glucose plasma levels in dogs, Int J. Pharm.23iS7-9S. 

Uses Cosmetic, pharmaceutical, and suppository formulation humectant, plasticizer in adhesives base for metal polishes lubricant for paper sizes inks in alkyd resins and coatings... 

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