Ramprakash Govindarajan

Ionization States in the Microenvironment of Solid Dosage Forms: Effect of Formulation Variables and Processing

PurposeEvaluation of the effect of formulation composition and processing variables on the microenvironment in solid dosage forms, based on ionization of indicator probes.Materials and MethodsSulfonephthalein indicators were intimately mixed with individual excipients, binary excipient mixtures or multi-component blends by the solvent deposition method. Diffuse reflectance visible spectroscopy of these solids provided a measure of indicator ionization extent. Indicator solution studies yielded equations relating solution pH to the ratio of the absorbance signals of the ionized to that of the unionized form, for each indicator. These equations and the spectral data of the indicator-treated solids were used to calculate an acidity function, ‘pHeq’ for the solids. The ionization of incorporated probes was also monitored during various stages of simulated pharmaceutical processing viz. wet and dry mixing.ResultsThe pHeq provided a measure of the physicochemical environment experienced by the probe in the solid. The surface nature of formulation components and their surface area available for interaction influenced the overall properties of the final blend. The extent of probe ionization varied at different stages of a simulated wet mixing–drying process. The pH of the excipient suspension was not a good predictor of the probe ionization in the final dried solid. Indicator ionization is expected to be influenced by the microenvironmental acidity, polarity and ionic strength. Individual excipient properties contributed to the overall microenvironment in powder mixtures even when dry mixed at low water contents.ConclusionsThe environment experienced by a drug in the final solid dosage form will be influenced by the nature of the excipients, the extent of their surfaces available for interaction, surface modification during processing and the amount and nature of solvent used.

Structure in Dehydrated Trehalose Dihydrate—Evaluation of the Concept of Partial Crystallinity

Purpose(i) To use trehalose as a model compound to evaluate the concept of crystallinity in pharmaceuticals. (ii) To understand the structural nature of dehydrated trehalose dihydrate.Materials and MethodsTrehalose dihydrate was dehydrated isothermally at several temperatures below 100°C and the anhydrous product was characterized by XRD, DSC and water vapor sorption.ResultsXRD and DSC suggested that the dehydration product was a partially crystalline α-polymorphic form of anhydrous trehalose % MathType!MTEF!2!1!+-% feaaeaart1ev0aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbbjxAHX% garmWu51MyVXgatuuDJXwAK1uy0HwmaeHbfv3ySLgzG0uy0Hgip5wz% aebbnrfifHhDYfgasaacH8qrps0lbbf9q8WrFfeuY-Hhbbf9v8qqaq% Fr0xc9pk0xbba9q8WqFfea0-yr0RYxir-Jbba9q8aq0-yq-He9q8qq% Q8frFve9Fve9Ff0dmeaabaqaciGacaGaaeqabaWaaeWaeaaakeaada% qadaqaaiaabsfadaWgaaWcbaGaeqySdegabeaaaOGaayjkaiaawMca% aaaa!3BC5!

Formulation Studies and In Vivo Evaluation of a Flurbiprofen-Hydroxypropyl β-Cyclodextrin System

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Investigation of Solution and Vapor Phase Mediated Phase Transformation in Thiamine Hydrochloride

. An increase in the temperature of dehydration resulted in a decrease in lattice order. In agreement with earlier findings, the ordered regions in the dehydrated lattice % MathType!MTEF!2!1!+-% feaaeaart1ev0aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbbjxAHX% garmWu51MyVXgatuuDJXwAK1uy0HwmaeHbfv3ySLgzG0uy0Hgip5wz% aebbnrfifHhDYfgasaacH8qrps0lbbf9q8WrFfeuY-Hhbbf9v8qqaq% Fr0xc9pk0xbba9q8WqFfea0-yr0RYxir-Jbba9q8aq0-yq-He9q8qq% Q8frFve9Fve9Ff0dmeaabaqaciGacaGaaeqabaWaaeWaeaaakeaada% qadaqaaiaabsfadaWgaaWcbaGaaeySdaqabaaakiaawIcacaGLPaaa% aaa!3B5D!

Impact of Freeze-Drying on Ionization of Sulfonephthalein Probe Molecules in Trehalose–Citrate Systems

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Processing-induced Phase Transformations and Their Implications on Pharmaceutical Product Quality

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The influence of measurement conditions on the Hammett acidity function of solid pharmaceutical excipients.

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