Karen M. Balwinski

Investigation of the Effect of Tablet Surface Area/Volume on Drug Release from Hydroxypropylmethylcellulose Controlled-Release Matrix Tablets

ABSTRACT The purpose of this study was to investigate the influence of tablet surface area/volume (SA/Vol) on drug release from controlled-release matrix tablets containing hydroxypropylmethylcellulose (HPMC). Soluble drugs (promethazine HCl, diphenhydramine HCl, and propranolol HCl) were utilized in this study to give predominantly diffusion-controlled release. Drug release from HPMC matrix tablets with similar values of SA/Vol was comparable within the same tablet shape (i.e., flat-faced round tablets) and among different shapes (i.e., oval, round concave, flat-faced beveled-edge, and flat-faced round tablets). Tablets having the same surface area but different SA/Vol values did not result in similar drug release; tablets with larger SA/Vol values had faster release profiles. Utility of SA/Vol to affect drug release was demonstrated by changing drug doses, and altering tablet shape to adjust SA/Vol. When SA/Vol was held constant, similar release profiles were obtained with f2 metric values greater than 70. Thus, surface area/volume is one of the key variables in controlling drug release from HPMC matrix tablets. Proper use of this variable has practical application by formulators who may need to duplicate drug release profiles from tablets of different sizes and different shapes.

Investigation of hypromellose particle size effects on drug release from sustained release hydrophilic matrix tablets.

Selected combinations of six model drugs and four hypromellose (USP 2208) viscosity grades were studied utilizing direct compression and in vitro dissolution testing. Experimental HPMC samples with differing particle size distributions (coarse, fine, narrow, bimodal) were generated by sieving. For some formulations, the impact of HPMC particle size changes was characterized by faster drug release and an apparent shift in drug release mechanism when less than 50% of the HPMC passed through a 230 mesh (63 μm) screen. Within the ranges studied, drug release from other formulations appeared to be unaffected by HPMC particle size changes.

Failure and deformation studies of syndiotactic polystyrene

Syndiotactic polystyrene (sPS) is a chemically resistant, high-heat, semicrystalline polymer which is currently under development by The Dow Chemical Co. The research reported herein was undertaken to determine the critical fracture strength, i.e., the critical stress intensity factor, K 1C , and the fracture energy, G 1C , of sPS. The studies were aimed at developing a basic understanding of the failure mechanism and toughness of sPS. This work included investigations of the effect of molecular weight, as well as flow-induced anisotropy. Scanning electron microscopy (SEM) was used to aid in the determination of the failure mechanism. During failure testing, it was observed that sPS fails with a slow, controlled crack growth and ruptures with an almost nondetectable amount of yielding, as based on a tensile dilatometry investigation and a plane strain, biaxial yield experiment. The proposed failure mechanism, based on the scanning electron micrographs, is one of constrained crazing, followed by void coalescence with the spherulite nucleators acting as stress concentrators in the system. The damage appears to be greatly confined, with little initial cold-drawing of the spherulites. Addition of a nucleator reduces the K 1C values somewhat, as added nucleation sites proliferate the sites for stress concentration across the sample.

Effect of Formulation Conditions on Hypromellose Performance Properties in Films Used for Capsules and Tablet Coatings

This study investigated the effects of polymer dispersion and hydration conditions on hypromellose (HPMC) film properties, such as strength, oxygen permeability, water vapor transmission, clarity, and haze. The focus of the study was to build a better understanding of the impact that changes to HPMC dispersion and hydration conditions have on performance properties of the resulting films. This understanding could potentially lead to more flexible formulation guidelines for formulators. Films of HPMC 2906 (USP) were produced from aqueous solutions prepared using various formulation conditions. Results showed that tensile properties and oxygen permeability were not significantly affected by the variables used. The differences observed in water vapor transmission are unlikely to affect practical application of the material. However, the differences observed in clarity and haze at 50°C hydration temperature could affect the appearance of a capsule or coated tablet. Several methods were used to determine whether loss of optical properties was due to surface phenomena or bulk defects within a film. Results indicated that the cloudy appearance was primarily due to surface roughness. Based on this information, there is some flexibility in formulation conditions; however, hydration temperatures greater than 25°C are not recommended.