Detection and Characterization of an Unknown Impurity in Levothyroxine Oral Solution Product: Implications for Formulation Development and Storage.

An existing USP(2010) impurity method for levothyroxine drug substance was modified to expand its applicability for the analysis of levothyroxine oral solution (OS) formulation while achieving desirable resolution between the components of OS formulation. When analyzed using modified USP(2010) method, an unknown impurity was detected in one of the levothyroxine OS products. A systematic investigation of unknown impurity was carried out using a combination of chromatographic, mass spectral and physicochemical methods to understand the nature of this unknown impurity.

Nucleophilic Addition in Aqueous Apomorphine Formulation Solutions in the Presence of Sodium Metabisulfite: Implications for Formulation Development and Manufacturing.

The purpose of this study was to investigate a potential nucleophilic addition mechanism in aqueous apomorphine formulation solutions in the presence of widely used antioxidants such as sodium metabisulfite (NaSO). The findings of this investigation provide insights into how sodium metabisulfite can influence the formation of particulate under the conditions leading to the auto-oxidation of apomorphine to apomorphine orthoquinone. The addition products resulting from the reaction of bisulfite nucleophile on apomorphine orthoquinone in a Michael addition fashion were identified and characterized using ultraviolet-visible spectroscopy and mass spectrometry.

In vitro methods can forecast the effects of intragastric residence on dosage form performance.

Intragastric conditions can affect the performance of solid dosage forms. For two cases, the ability of in vitro methods to forecast these effects was investigated: first, the ability of cholestyramine to sequester bile salts in the fed small intestine and, second, disintegration times of hard gelatin capsules. After incubating cholestyramine for 90 min in milk gradually digested with pepsin, the binding of taurocholates from fed state simulating intestinal fluid onto the resin became non-specific and the affinity constant was reduced from 220 l/mole (without prior incubation) to 60 l/mole.

Gamma scintigraphy for testing bioequivalence: a case study on two cromolyn sodium nasal spray preparations.

The present work was carried out to study the deposition patterns and clearance of technetium-99m (99mTc) DTPA labeled cromolyn sodium (CS) solutions when administered from two different CS nasal products using gamma scintigraphy. Five healthy volunteers received a single dose with complete crossover design involving treatment A (test formulation) and treatment B (reference formulation). The deposition patterns as well as the changes in distribution of the radiolabeled CS solutions due to the mucociliary transport were monitored by gamma scintigraphy.

Vaginal distribution of Replens and K-Y Jelly using three imaging techniques.

Background: Determination of vaginal distribution is important to the development of potential vaginal microbicidal or spermicidal products.

Study Design: This was a descriptive study of three imaging techniques with a randomized crossover assignment of two gels and activity status within each technique.

Method: Each of three sites utilized one technique.

Coprecipitation of nonoxynol-9 with polyvinylpyrrolidone to decrease vaginal irritation potential while maintaining spermicidal potency.

The aim of this study was to test the hypothesis that polyvinylpyrrolidone (PVP) would increase the critical micelle concentration (CMC) of nonoxynol-9 (N-9), providing a reduction in its irritation potential, while maintaining essential spermicidal activity. Solid coprecipitates of N-9 with PVP were manufactured with the use of a modified lyophilization process. The irritation potential of N-9 was estimated by an in vitro assay, monitoring the extent of hemolysis of red blood cells.

Kinetics of paclitaxel 2'-N-methylpyridinium mesylate decomposition.

This study was designed to examine the kinetics of decomposition of paclitaxel 2'-N-methylpyridinium mesylate (PNMM), a derivative of paclitaxel. Further, the potential for PNMM to act as a prodrug of paclitaxel was assessed in vitro. Stability studies of PNMM were conducted over a pH range of 4.

Evaluation of the in vivo disintegration of solid dosage forms of a bile acid sequestrant in dogs using gamma-scintigraphy and correlation to in vitro disintegration.

Purpose: [corrected] To evaluate the in vivo disintegration behavior of tablets and capsules of a bile acid sequestrant, DMP 504, in beagle dogs and to assess the significance of the in vitro disintegration of the dosage forms on subsequent in vivo behavior in order to draw possible in vitro-in vivo correlations.

Methods: Tablet and capsule formulations of a bile acid sequestrant, DMP 504, were formulated with samarium oxide and neutron activated to produce radioactive 53Sm to noninvasively evaluate their in vivo behavior in beagle dogs by gamma-scintigraphy. A four-way crossover design was completed (n = 4) in which (a) tablets from two different batches were administered under the fasted condition and manufactured using different lots of drug substance where one batch exhibited relatively faster in vitro disintegration time (30 min) than the other tablet batch, which resulted in slower disintegration (45 min), (b) a capsule formulation was administered to fasted beagles, and (c) the tablet having slower in vitro disintegration was also administered in the fed state, and its in vivo disintegration was compared to that observed in the fasted state.

Synthesis of novel iodinated derivatives of nonoxynol-9 and their bioavailability in rats.

The absorption and distribution of iodinated derivatives of nonoxynol-9, after vaginal administration in rats, were compared with results reported for [14C] nonoxynol-9. Mono-iodinated nonoxynol-9 was synthesized in addition to the radiolabeled derivative incorporating iodide-125 ([125I]). Six hours after dosing, test rats were euthanized and selected tissues were excised and assessed for radioactivity.