Suppositories, analysis

Massaccesi reported the development of a two-phase titration method for the analysis of miconazole and other imidazole derivatives in pure form and in pharmaceutical formulation [14], To the sample (10 mg) are added 10 mL of water, 10 mL of 1 M-sulfuric acid, 25 mL of dichloromethane and 1 mL of 0.05% indophenol blue (C.I. No. 49700) in dichloromethane solution and the solution is titrated with 10 mM sodium dodecyl sulfate until the color of the organic phase changes from blue to pale yellow. Results obtained for the drug in pure form, tablets, suppositories, cream and lotion agreed with the expected values and the coefficient of variation (n = 6) were 0.3-0.35%. Imidazole and the other constituents of the pharmaceutical preparations did not interfere. 

System (6) was recommended for the analysis of hydrocortisone, cortisone, and their acetates in pharmaceutical preparations, as well as their separation from a number of impurities and decomposition products [154]. The sample (creams, ointments, lotions, or suppositories) was extracted with hot ethanol prior to introduction into the HPLC system. 

After an extraction into methylene chloride from a methanolic pH 7.2 phosphate buffer, the ultraviolet absorbance is measured near 318 nm. This analysis measures intact indomethacin in the presence of its hydrolytic degradation products. If esterification has occurred, an ether wash prior to extraction from phosphate buffer has been used to prevent interference caused by esters(39). This procedure is also applicable to injections, suppositories, suspensions and tablets. 

In aqueous methanol, indomethacin exhibits a half-wave potential (E.,-) at the droning mercury electrode which is dependent upon pH. In 0.1M methanolic lithium chloride, indomethacin has two waves between -1.4v and -1.6v (vs. S.C.E.). The first step height is diffusion controlled and corresponds to a two electron reduction of the amide carbonyl. The second wave is believed to be a kinetic wave. The method as described is specific for nonhydrolyzed indomethacin and is suitable for analysis of capsules, suppositories and suspensions with precision of +1.2%, +0.7% and +1.2% for the respective formulations(43). 

The development of a standarized analysis strategy using ion-pair extraction from basic drugs have been reported [23]. This approach has been used to assay basic drugs in syrups, ointments, emulsions, and suppositories. Ion-pair formation with tri- -octylamine extracted colorants from syrups, oral suspension, tablets, gelatin capsules, suppositories, and granules [25]. 

The base used in the formulation of suppositories can often affect the rate of decomposition of the active ingredients. Aspirin decomposes in several polyoxyethylene glycols which are often incorporated into suppository bases. Degradation was shown to be due in part to transesterification, giving the decomposition products salicylic acid and acetylated polyethylene glycol. The rate of decomposition, which followed pseudo first-order kinetics, was considerably greater than when a fatty base such as cocoa butter was used. Analysis of commercial batches of 100 mg indometacin-polyethylene glycol... 

An example from pharmaceutical quahty control can serve as a model here. In the analysis of suppositories, the matrix components (e.g. wax) are displaced by a nonpolar solvent for a few centimeters beyond the solvent front of the subsequent chromatography of the substance, and this can then proceed through the matrix without further problems. Figure 65 shows the chromatogram of GastrosU suppositories (active substance metoclopramide base) after derivatization in an iodine chamber. The matrix components are clearly visible in the upper part of the plate. 

The determination of the dissolution rate of the active substance from the dosage form is relevant for solid dosage forms and dispersions, especially when the substance is poorly soluble (see Sect. 16.1.4). Only dissolved substances are available for absorption. Ph. Eur. describes in chapter 2.9.3 Dissolution test for solid dosage forms the equipment, the method of analysis and the interpretation of the determination of the dissolution rate of tablets and capsules. For suppositories it is described in Ph. Eur. chapter 2.9.42 Dissolution test for lipophilic solid dosage forms . 

The standard method of analysis for these products is microbiological and gives a rather large deviation between replicates. Several fluorometric and colorimetric procedures have appeared in the literature, but all are time consuming and have only fair accuracy. Nonaqueous titrimetric methods were developed in our laboratory which could be applied successfully to tablets, capsules, ointments, parenterals, and suppositories with an accuracy of about iO.Sfo. Comparative results are shown in Table XVIII. 

Uses High-grade lubricating oil perfume fixing agent, lubricant in toiletries, cosmetics gas chromatographic analysis transformer oil in watch and chronometer oils vehicle, emollient, skin lubricant in cosmetics and phannaceuticals carrier of lipid-sol. drugs in suppositories ointment base moisturizer bactericide... 

In many ways pharmaceutical dosage forms can be regarded as dispersions of drugs in carriers. Whereas this is utilised in solid dispersions, it is equally applicable to suppositories or pessaries, or indeed any system where heat (or solvent and subsequent evaporation) is used to produce a dispersion of a drug in a carrier. Thermal analysis, and especially DSC, can be used to measure the development of structure or subsequent storage. This can be reflected as an increase in fusion enthalpy on storage [110, 111] of solid dispersions, or conversion of the crystalline form, whether polyethylene glycol [110] or as a... 

This is a broad area of thermal analysis, samples ranging from the triglycerides and polyethylene glycols that are the basis of pessaries and suppositories, through to formulated creams and ointments. 

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