Development of a Kinetic Model to Investigate the Effect of Compositional Variation and a Processing Condition on the Solid-State Degradation of Gabapentin

Gabapentin is used in the treatment of seizures and neuropathic pain. Gabapentin undergoes intra-molecular cyclization to form a γ-lactam. The product lactam is twenty times more toxic than gabapentin, causing seizures in animal models. The United States Pharmacopeia (USP) limits the content of lactam in gabapentin formulations to 0.4% w/w. A number of patents have been issued for solid dosage forms formulated to stabilize gabapentin. Despite these efforts, factors contributing to gabapentin’s poor stability in the solid-state have not been explored completely. It was hypothesized, that physicochemical properties of the excipients and compaction pressure will accelerate the solid-state degradation of gabapentin, increasing the kinetic rate constant for lactam formation. To test the hypotheses, binary mixtures and compacts of gabapentin with different excipients were prepared and stored under accelerated study conditions. The concentration of lactam and gabapentin was measured using a validated analytical method. A concentration dependent catalytic effect by the excipients was determined by mixing different concentrations of the excipient with gabapentin. The effect of excipient particle size was determined by mixing different size fractions of the excipient with gabapentin. Significant degradation of unprocessed gabapentin in the presence of excipients strongly suggested a catalytic role of the excipients on gabapentin’s degradation. The existing model was expanded to account for the observed catalytic effect of excipients. A relationship was developed between the rate constant for lactam formation and physical properties of the excipients (such as particle size, morphology, molecular weight, molecular cross sectional area and specific surface area). Along with the catalytic effect of the excipients, compaction pressure and powder properties of the excipients such as moisture content, particle size and yield pressure appeared to be other potential contributing factors affecting gabapentin’s degradation

The reliability of a structured examination protocol and self administered vaginal swabs: a pilot study of gynaecological outpatients in Goa, India.

OBJECTIVES: Low participation rates for gynaecological examination and low reliability of clinical reporting of gynaecological examination findings are problems in community studies of gynaecological morbidity in India. This pilot study aimed to describe the reliability of a new examination protocol for recording the findings of gynaecological examination and the reliability and acceptability of the use of self administered vaginal swabs for the diagnosis of reproductive tract infections. METHOD: 75 women attending a gynaecology outpatient clinic were purposively sampled. Each woman was examined by two gynaecologists independently who recorded findings on the new examination protocol. Two swabs were collected from each woman, one by the gynaecologist and one by the woman. Swabs were smeared on separate slides which were stained and read for bacterial vaginosis and candidiasis by laboratory technicians blind to the mode of collection of the slides. RESULTS: The study showed a high inter-rater reliability for most of the items of the examination protocol. The interslide agreement for the diagnosis of the two RTIs was high. One third of women preferred the self administered swab. CONCLUSIONS: The examination protocol is a reliable method of recording gynaecological examination findings, and self administered swabs a useful way of obtaining vaginal specimens from women who did not wish to undergo gynaecological examinations in studies in the Indian setting

Efficiency effects on coalition formation in contests

This paper studies the problem of endogenous coalition formation in contests: how players organize themselves in groups when faced with the common objective of securing a prize by exerting costly effort. The model presented adopts an axiomatic approach by assuming certain properties for the winning probability that imply efficiency gains from cooperation in contest settings. Efficiency gains are said to be generated if any coalition experiences increasing marginal returns with aggregate effort until a threshold. These properties identify a wide class of generalised Tullock contest success functions. We analyse a sequential coalition formation game for an arbitrary number of symmetric players and exogenous effort. If coalitions generate sufficient efficiency gains, then any equilibrium always consists of two or more coalitions where at least two coalitions are of unequal size. This result extends to endogenous efforts if the cost functions are sufficiently convex

Mergers and innovation portfolios

© 2022 The Authors. The RAND Journal of Economics published by Wiley Periodicals LLC on behalf of The RAND Corporation.This article studies mergers in markets where firms invest in a portfolio of research projects of different profitability and social value. The investment of a firm in one project imposes both a negative business-stealing and a positive business-giving externality on the rival firms. We show that when the project that is relatively more profitable for the firms appropriates a larger (smaller) fraction of the social surplus, a merger increases (decreases) consumer welfare by reducing investment in the most profitable project and increasing investment in the alternative project. The innovation portfolio effects of mergers may dominate the usual market power effects

Mergers and Innovation Portfolios

© 2022 The Authors. The RAND Journal of Economics published by Wiley Periodicals LLC on behalf of The RAND Corporation.This article studies mergers in markets where firms invest in a portfolio of research projects of different profitability and social value. The investment of a firm in one project imposes both a negative business-stealing and a positive business-giving externality on the rival firms. We show that when the project that is relatively more profitable for the firms appropriates a larger (smaller) fraction of the social surplus, a merger increases (decreases) consumer welfare by reducing investment in the most profitable project and increasing investment in the alternative project. The innovation portfolio effects of mergers may dominate the usual market power effects