Method to recover a lipophilic drug from hydroxypropyl methylcellulose matrix tablets.

A reverse-phase high-performance liquid chromatographic (HPLC) method for recovery of the lipophilic drug, alprazolam, from matrix tablets containing the hydrophilic polymer hydroxypropyl methylcellulose (HPMC) was developed. Lipophilic drugs, such as alprazolam, are difficult to completely extract and quantitate from tablets containing HPMC polymer. The percentage of recoveries of alprazolam from placebo powder spiked with alprazolam stock solution and from placebo powder mixed with alprazolam powder were about 100% and 85% to 95%, respectively. The validated method using water to completely dissolve HPMC before the addition of a strong solvent to dissolve and extract the drug from the HPMC solution was shown to be the most reproducible method. Different molecular weight distributions of the HPMC polymer, such as HPMC-K4M and HPMC-K100LV, did not influence the dissolution results of alprazolam using this validated method. Similarly, the excipients composing the matrix tablet formulations, such as dicalcium phosphate dihydrate, dicalcium phosphate anhydrous, calcium sulfate dihydrate, sucrose, dextrose, and lactose monohydrate, did not influence the percent recovery of alprazolam. The recovery method reported herein was shown to be the most efficient to achieve complete recovery of alprazolam from powder blends and tablets containing a variety of excipients and different grades of HPMC.

Trends in antifungal research.

With the increasing use of aggressive immunosuppressive therapies in the management of a variety of patient populations, the continuing presence of the AIDS pandemic and the therapeutic advances employed in critical care settings, an increasing number of serious fungal infections are being encountered by today's practicing clinicians. Traditionally, antifungal drug therapy has been delivered by means of intravenous infusion, oral administration, or topical application. Recently, a number of alternative routes of antifungal drug delivery have been developed and investigated, and the traditional means of antifungal administration have been improved to facilitate the therapeutic use of new and reformulated antifungal agents. Organized based on the route of administration, this chapter reviews these advances in antifungal drug delivery.

Characterization of an inclusion complex of cholesterol and hydroxypropyl-beta-cyclodextrin.

Interactions between endogenous cholesterol and cyclodextrins have been investigated by several researchers, and they found altered skin penetration of some drugs, membrane disruption, and extraction of cholesterol from the large lipoprotein particles or animal fat. In the present study, an inclusion complex composed of cholesterol and hydroxypropyl-beta-cyclodextrin (HPbetaCD) prepared by lyophilization was investigated and characterized in order to confirm these interactions. Five grams of cholesterol were dispersed in 50 ml of 73.2 mM HPbetaCD aqueous solution, mixed for 2 days, and the filtrate lyophilized. A phase solubility study was performed by mixing an excess amount of cholesterol with an aqueous solution containing increasing amounts of HPbetaCD. The amount of cholesterol in solution after mixing for 2 days at 25 degrees C was determined by HPLC. The inclusion complex was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry, and differential scanning calorimetry (DSC). An Ap-type Higuchi phase solubility diagram, DSC, FTIR, and X-ray diffraction demonstrated the formation of an inclusion complex. DSC thermograms indicated that the endothermic peaks of cholesterol and physical mixture of cholesterol with HPbetaCD due to the fusion of drug crystals, were absent in DSC thermograms obtained on the freeze dried inclusion complex. FTIR spectra indicated that some of the absorption peaks in the lyophilized inclusion complex were different from that of the physical mixture of cholesterol and HPbetaCD. X-ray diffraction patterns showed that the pure cholesterol and a physical mixture of cholesterol and HPbetaCD exhibited crystalline characteristics whereas the lyophilized inclusion complex and HPbetaCD displayed amorphous characteristics. The results indicated that the formation of a cholesterol/HPbetaCD inclusion complex is more water soluble than cholesterol alone.

Preformulation studies on Freund's incomplete adjuvant emulsion.

Freund's Incomplete Adjuvant (FIA), which is used in vaccine therapy, is a water-in-oil emulsion delivery system consisting of an aqueous internal phase containing an antigenic protein dispersed in an external phase containing a mixture of mannide monooleate and light mineral oil. Preformulation studies are reported in this investigation for FIA emulsion. The preformulation studies included the determination of the critical micelle concentration (CMC) of the formulations investigated, the surface activity of mannide monooleate at the interface between the oil phase and the aqueous phase containing ovalbumin as the model antigenic protein, and the effect of ovalbumin on the surface activity at the interface. The influence of the concentration of mannide monooleate and/or ovalbumin on the interfacial tension between light mineral oil and either purified water or 0.9% w/v normal saline solution was measured by the DuNouy Ring Method at 25 degrees C. The CMC was determined experimentally from the relationship between the concentration of the surface active agent in each formulation and the interfacial tension. The number of moles of the surface active agent per unit area at the interface (surface excess concentration) was calculated from the Gibbs' Adsorption equation. The results indicated that mannide monooleate was an effective surface active agent since the formulation containing only mannide monooleate provided the lowest magnitude of CMC. The presence of the surface active agent, mannide monooleate and/or ovalbumin, in the formulations studied reduced the interfacial tension between the two phases. The surface activity was influenced by the presence of an electrolyte (sodium chloride), a protein (ovalbumin), or mannide monooleate in the formulation. The presence of antigenic proteins in the aqueous phase of a waterin-oil emulsion influenced the effectiveness of a surface active agent in the formulation.

Determination of diazolidinyl urea in a topical cream by high-performance liquid chromatography.

A high-performance liquid chromatographic method for the determination of diazolidinyl urea (DU) in a cream formulation is described. The aqueous phase of the emulsion was separated by centrifugation, removed, filtered, diluted and applied onto the HPLC system. DU was detected by ultraviolet absorption at a wavelength of 214 nm. The calibration curve was linear over the range of 79-553 micrograms/ml, and identical when determined on consecutive days. The relative standard deviation for repeat determinations was less than 0.5%. Recoveries were 97.74-101.72%. This analytical method is useful for quantitation of DU in cream formulations.