Ali R. Rajabi-Siahboomi

Influence of drug:hydroxypropylmethylcellulose ratio, drug and polymer particle size and compression force on the release of diclofenac sodium from HPMC tablets

This study evaluates the relationship and influence of formulation and technological factors such as drug:hydroxypropylmethylcellulose (HPMC) ratio, particle size of the drug, particle size of HPMC and compression force, on drug release from matrices containing HPMC and diclofenac sodium as a model drug. The influence of these variables was assessed by multi-way analysis of variance. The results of the present study point out that the rate and mechanism of diclofenac sodium release from HPMC K15M matrices are mainly controlled by the drug:HPMC ratio. The drug and HPMC particle size also influence the drug release parameters, although to a lesser extent. Finally, the independence of the drug release from matrix tablets with respect to the compression force is reported.

Structure and behaviour in hydrophilic matrix sustained release dosage forms: 2. NMR-imaging studies of dimensional changes in the gel layer and core of HPMC tablets undergoing hydration

Abstract The swelling of hydrating HPMC tablets has been studied by NMR microscopy. The technique is non-invasive and has allowed both dimensional changes in the core and in the developing surface hydrated layer to be studied. Hydration at the edges of the tablet occurred to a greater extent than in the centre of the table surfaces, giving rise to a convex shaped hydrated layer. Gel layer development occurred to the same extent in both axial and radial directions, and was similar in all HPMC types. The predominantly axial swelling reported for all HPMC types, was shown to result almost equally from growth of the hydrated surface gel layer and expansion of the ungelled tablet core. The smaller axial expansion observed in E4M tablets was not a result of slower gel layer growth, but was entirely due to a smaller expansion of the core.

Structure and Behavior in Hydrophilic Matrix Sustained Release Dosage Forms: 4. Studies of Water Mobility and Diffusion Coefficients in the Gel Layer of HPMC Tablets Using NMR Imaging

AbstractPurpose. The purpose of this study was to characterise the water mobility in the gel layer of hydrating HPMC tablets. Water mobility in the gel layer of different HPMCs was studied. Methods. NMR imaging, a non-invasive technique, has been used to measure the spatial distribution of self-diffusion coefficient (SDC) and T2 relaxation times across the gel layer. Results. It has been shown that there is a water mobility gradient across the gel layer of HPMC tablets. Although SDC and T2 relaxation times in the outer parts of the gel layer approached that of free water, in the inner parts they decreased progressively. Water mobility and SDC in the gel layer of different HPMCs appeared to vary with degree of substitution of the polymer and the lowest values were obtained across the gel layer of K4M tablets. Conclusions. Water mobility varies across the gel layer of hydrating HPMC tablets and it is dependent on the degree of substitution of the polymer.

Crystal Habit Modifications of Ibuprofen and Their Physicomechanical Characteristics

Ibuprofen was crystallized from methanol, ethanol, isopropanol, and hexane at similar conditions. Marked differences in crystal habit of the samples obtained from these solvents were observed. The samples crystallized from methanol and ethanol had a polyhedral crystal habit, while those from hexane were needlelike. Those from isopropanol were elongated crystals. X-ray powder diffraction (XPD) and differential scanning calorimetry (DSC) studies confirmed that these samples were structurally similar; therefore, polymorphic modifications were ruled out. The results showed that crystal habit modification had a great influence on the mechanical properties (compressibility, flow rate, and bulk density) of ibuprofen crystals. Samples obtained from methanol and ethanol exhibited the highest bulk density and the best flow rate, while those from hexane showed the lowest bulk density and the worst flow rate. The samples obtained from ethanol exhibited the best compression force/hardness profiles, and those obtained from hexane produced the softest tablets.

Release of Propranolol Hydrochloride from Matrix Tablets Containing Sodium Carboxymethylcellulose and Hydroxypropylmethylcellulose

Hydroxypropylmethylcellulose (HPMC) and three viscosity grades of sodium carboxymethylcellulose (NaCMC), namely NaCMC (Blanose 7H 4XF), NaCMC (Courlose P 800), and NaCMC (Courlose P 350), were investigated for their ability to provide a sustained release of propranolol hydrochloride from matrices. The rank order of release rate, in the absence of HPMC, was NaCMC (Blanose) < NaCMC P 800 < NaCMC P 350 for matrices containing 95-285 mg NaCMC, and was dependent on their viscosity grades. The effects of changing the ratio of HPMC to NaCMC (Blanose) and the drug/total polymer ratio were examined. The release rates decreased as the proportion of NaCMC in the matrices increased. Zero-order release of propranolol hydrochloride was obtained from matrices containing 285 mg 3:1 NaCMC (Blanose)/HPMC. Differential scanning calorimetry was used to quantify the moisture uptake by the polymers at 37 degrees C. Wafers containing NaCMC (Blanose) or 1:1 HPMC/NaCMC (Blanose) absorbed water similarly. A study of the erosion rates of matrices containing polymer only indicated that NaCMC (Blanose) eroded more quickly than HPMC. When propranolol hydrochloride was included in matrices containing NaCMC (Blanose), the erosion was reduced as a result of the insolubility of a complex formed between NaCMC and propranolol hydrochloride. The interaction between propranolol hydrochloride and NaCMC (Blanose) was confirmed by both dialysis and by monitoring the release of sodium ions from the matrices.

A study on the interaction of water and cellulose ethers using differential scanning calorimetry

Abstract Differential scanning calorimetry (DSC) has been used to examine the distribution of water within hydroxypropylmethylcellulose 2208 (HPMC K15M) gels. Thermal events were apparent in the DSC scans of HPMC K15M gels which were dependent on their storage time, the concentration of the polymer and the cooling and heating rates utilised during DSC. Two or more thermal events were present on the low temperature side of the melting endotherm for gels (20–35% w/w HPMC K15M) in the −15 to 0°C range. These may indicate the presence of different types of water in the gels. The number of moles of non-freezing water per polymer repeating unit HPMC K15M was estimated for gels as ∼8 mol after 24 h and ∼3.8 mol after 96 h storage. It is suggested that hydrating water is released from the polymer during equilibration between 24 and 96 h storage.

Magnetic resonance imaging of controlled release pharmaceutical dosage forms

Magnetic resonance imaging offers us a powerful non-invasive method for picturing events inside controlled-release dosage forms. It allows us to observe, follow and measure important processes, such as hydration and diffusion, that can contribute directly to the process of drug release. The potential of this technique for increasing our understanding of drug release mechanisms, and the behaviour of dosage forms in vitro and in vivo is only beginning to be exploited. The unique information obtained from MRI studies will provide important detailed knowledge in problem solving and formulation development.

Formation and compression characteristics of prismatic polyhedral and thin plate-like crystals of paracetamol.

Prismatic polyhedral crystals of paracetamol were prepared by cooling an aqueous saturated solution of paracetamol from 65 to 25 degrees C. Thin plate-like crystals were prepared by adding a concentrated solution of paracetamol in hot ethanol to water at 3 degrees C. Infrared (IR), X-ray powder diffraction (XPD) and differential scanning calorimetry (DSC) studies confirmed that these two forms of crystals were structurally similar, therefore polymorphic modifications were ruled out. The crystal habit influenced the compression properties during axial compression of paracetamol at different constant rates in a compaction simulator, the Heckel plots and their associated constants being dependent on the habits. The correlation coefficient of the initial part of the Heckel plots, and also the values of strain rate sensitivity (SRS), were lower for thin plate-like crystals, indicative of greater fragmentation for the thin plate-like as compared to polyhedral crystals. Compacts made from thin plate-like crystals exhibited higher elastic recoveries and elastic energies indicating that these crystals underwent less plastic deformation during compression than the polyhedral crystals.

NMR microscopy of hydrating hydrophilic matrix pharmaceutical tablets

NMR microscopy has been used to monitor the formation of the gel layer in hydrating hydrophilic polymer tablets. Such tablets are used in the controlled delivery of drugs, where it has been found that the rate and extent of the swelling of the outer gel layer critically influences the kinetics of drug release. Tablets were hydrated in distilled water at 37 degrees C and then imaged at discrete time intervals using a 500 MHz microscope. The growth of the gel layer was clearly observed in time sequences of radial and axial sections. Axial images showed some interesting dimensional changes, with the gel at the flat surface of the tablet developing a concave shape. This is probably a reflection of the occurrence of uni-axial stress relaxation as hydration proceeds. Diffusion- and T2-weighted images provided evidence that the water in the gel layer is more strongly bound close to the dry core of the tablet than at the more fully hydrated outer surface. In images of tablets containing diclofenac, disruption of the gel layer was shown to occur primarily from the flat surfaces of the tablet, whilst the distribution of particles could be seen in tablets doped with insoluble calcium phosphate.

Highly compressible paracetamol: I: crystallization and characterization.

It was found that polyvinylpyrrolidone (PVP) is an effective additive during crystallization of paracetamol and significantly influenced the crystallization and crystal habit of paracetamol. These effects were attributed to adsorption of PVP onto the surfaces of growing crystals. It was found that the higher molecular weights of PVP (PVP 10000 and PVP 50000) were more effective additives than lower molecular weight PVP (PVP 2000). Paracetamol particles obtained in the presence of 0.5% w/v of PVP 10000 or PVP 50000 had near spherical structure and consisted of numerous rod-shaped microcrystals which had agglomerated together. Particles obtained in the presence of PVP 2000 consisted of fewer microcrystals. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XPD) experiments showed that paracetamol particles, crystallized in the presence of PVP, did not undergo structural modifications. By increasing the molecular weight and/or the concentration of PVP in the crystallization medium the amount of PVP incorporated into the paracetamol particles increased. The maximum amount of PVP in the particles was 4.32% w/w.