Sarsvatkumar Patel

Lubrication Potential of Magnesium Stearate Studied on Instrumented Rotary Tablet Press

The aim of this study was to investigate the lubrication potential of 2 grades of magnesium stearate (MS) blended with a mix of dicalcium phosphate dihydrate and microcrystalline cellulose. Force-displacement, force-time, and ejection profiles were generated using an instrumented rotary tablet press, and the effect of MS mixing time (10, 20, and 30 minutes) and tableting speed (10.7, 13.8, and 17.5 rpm) was investigated. The packing index (PI), frictional index (FI), and packing energy (PE) derived from the force-displacement profiles showed that MS sample I performed better than sample II. At higher lubricant mixing times, the values of PI were observed to increase, and values of FI and PE were observed to decrease for both MS samples. Lower values of area under the curve (AUC) calculated from force-time compression profiles also showed sample I to be superior to sample II in lubrication potential. For both the samples, the values of AUC were observed to decrease with higher lubricant mixing times. Tapping volumetry that simulates the initial particle rear-rangement gave values of parameter a and Cmax that were higher for sample I than sample II and also increased with lubricant mixing time. The superior lubrication potential of sample I was also established by the lower values of peak ejection force encountered in the ejection profile. Lower ejection forces were also found to result from higher tableting speeds and longer lubricant mixing times. The difference in lubrication efficacy of the 2 samples could be attributed to differences in their solid-state properties, such as particle size, specific surface area, and d-spacing.

Compaction behavior of roller compacted ibuprofen

The effect of roller compaction pressure on the bulk compaction of roller compacted ibuprofen was investigated using instrumented rotary tablet press. Three different roller pressures were utilized to prepare granules and Heckel analysis, Walker analysis, compressibility, and tabletability were performed to derive densification, deformation, course of volume reduction and bonding phenomenon of different pressure roller compacted granules. Nominal single granule fracture strength was obtained by micro tensile testing. Heckel analysis indicated that granules prepared using lower pressure during roller compaction showed lower yield strength. The reduction in tabletability was observed for higher pressure roller compacted granules. The reduction in tabletability supports the results of granule size enlargement theory. Apart from the granule size enlargement theory, the available fines and relative fragmentation during compaction is responsible for higher bonding strength and provide larger areas for true particle contact at constant porosity for lower pressure roller compacted granules. Overall bulk compaction parameters indicated that granules prepared by lower roller compaction pressure were advantageous in terms of tabletability and densification. Overall results suggested that densification during roller compaction affects the particle level properties of specific surface area, nominal fracture strength, and compaction behavior.

Mechanistic investigation on pressure dependency of Heckel parameter.

This work proposed to study the influence of varying compaction pressure on the plastic energy, elasticity (Youngs modulus), particle yield strength, strain hardening, and applied pressures on derived Heckel parameter using material with different densification and deformation mechanisms: ibuprofen (IBN), paracetamol (PCM) (elastic behavior), methyl cellulose (Me-Cel), microcrystalline cellulose (MCC), sodium chloride (NaCl) (plastic behavior), and dicalcium phosphate (DCP) (brittle fracture). Force-displacement data were captured during in-die compaction for all materials having different deformation behavior. The apparent mean yield pressure (Py), plastic energy, Youngs moduli, strain hardening parameter and rate of increase in Py were calculated from force-displacement compaction profiles obtained across a pressure range of 65-260 MPa. Materials under confined compression loading showed pressure dependent biphasic behavior in Py upon increasing pressure from 65 MPa to 260 MPa. IBN and PCM showed pressure dependency due to simultaneous elasticity and strain hardening upon increasing applied pressure. Me-Cel, MCC, and NaCl showed lower pressure dependency while DCP showed higher change in Py upon increasing pressure as a result of higher yield strength of DCP particles. Apparent mean yield pressure from Heckel analysis was significantly affected by the applied pressure, viscoelastic behavior, particle yield strength, and strain hardening. The simultaneously occurring events of elastic deformation and strain hardening give a false increase in Py at higher applied pressures.

Prediction of mechanical properties of compacted binary mixtures containing high-dose poorly compressible drug

The aim of the study was to develop, compare and validate predictive model for mechanical property of binary systems. The mechanical properties of binary mixtures of ibuprofen (IBN) a poorly compressible high dose drug, were studied in presence of different excipients. The tensile strength of tablets of individual components viz. IBN, microcrystalline cellulose (MCC), and dicalcium phosphate dihydrate (DCP) and binary mixtures of IBN with excipients was measured at various relative densities. Prediction of the mechanical property of binary mixtures, from that of single components, was attempted using Ryshkewitch-Duckworth (R-D) and Percolation theory, by assuming a linear mixing rule or a power law mixing rule. The models were compared, and the best model was proposed based on the distribution of residuals and the Akaikes information criterion. Good predictions were obtained with the power law combined with linear mixing rule, using R-D and Percolation models. The results indicated that the proposed model can well predict the mechanical properties of binary system containing predominantly poorly compressible drug candidate. The predictions of these models and conclusions can be systematically generalized to other pharmaceutical powders.

Effect of sample preparation method on quantification of polymorphs using PXRD.

The purpose of this study was to improve the sensitivity and accuracy of quantitative analysis of polymorphic mixtures. Various techniques such as hand grinding and mixing (in mortar and pestle), air jet milling and ball milling for micronization of particle and mixing were used to prepare binary mixtures. Using these techniques, mixtures of form I and form II of clopidogrel bisulphate were prepared in various proportions from 0–5% w/w of form I in form II and subjected to x-ray powder diffraction analysis. In order to obtain good resolution in minimum time, step time and step size were varied to optimize scan rate. Among the six combinations, step size of 0.05° with step time of 5 s demonstrated identification of maximum characteristic peaks of form I in form II. Data obtained from samples prepared using both grinding and mixing in ball mill showed good analytical sensitivity and accuracy compared to other methods. Powder x-ray diffraction method was reproducible, precise with LOD of 0.29% and LOQ of 0.91%. Validation results showed excellent correlation between actual and predicted concentration with R2 > 0.9999.

Phase behavior, intermolecular interaction, and solid state characterization of amorphous solid dispersion of Febuxostat.

Abstract The aim of this work was to prepare and characterize the amorphous molecular dispersion of Febuxostat (FXT) using PVP K30, HPMC-AS, Soluplus®, and PVP VA64. The solid dispersions were prepared by solvent evaporation technique. Their physical properties were studied by differential scanning calorimetry, powder X-ray diffraction, Fourier transformation infrared spectroscopy, and compared to that of same physical mixtures. The success of physicochemical stability of the dispersions is often revealed as glass transition temperature (Tg) versus composition (w) dependencies. The shape of the Tg versus composition was mathematically modeled using the Gordon–Taylor equation, Couchman–Karasz equation, Brekner–Schneider–Cantow equation, and a three-parameter BCKV equation. In this work, different types of Tg patterns obtained for FXT–polymer binary mixtures are analyzed in terms of the above equations and relations between their prime fitting parameters are presented. The theoretical values and modeled parameters were compared using various results obtained by thermal analysis. The influence of important physicochemical phenomena and properties of the mixtures on the shape of the Tg versus composition patterns are also illustrated. The interaction between drug and polymers and the model parameters were analyzed, aiming to assess the state of mixing and intermolecular interactions.

Characterization and Thermodynamic Relationship of Three Polymorphs of a Xanthine Oxidase Inhibitor, Febuxostat

Febuxostat (FXT), a xanthine oxidase inhibitor, is an interesting and unique molecule, which exhibits extensive polymorphism, with over 15 polymorphic forms reported to date. The primary purpose of the study was to characterize the three polymorphic forms with respect to their thermodynamic quantities and establish thermodynamic relationship between them. The polymorphs were characterized by thermal and powder X-ray diffraction methods. Three different methods were used to calculate the transition temperatures (Ttr) and thereby their thermodynamic relationships. Although the first and second method used calorimetric data (melting point and heat of fusion), the third method employed the use of configurational free energy phase diagram. The onset melting points of three polymorphic forms were found to be 482.89 ± 0.37 K for form I, 476.30 ± 1.21 K for form II, and 474.19 ± 0.11 K for form III. Moreover, the powder X-ray diffraction patterns for each form were also unique. The polymorphic pair of form I and II and of form I and III was found to be enantiotropic, whereas pair of form II and III was monotropic. Besides the relative thermodynamic aspects (free energy differences, enthalpy, entropy contributions) using different methods, the pharmaceutical implications and phase transformation aspects have also been covered.