Isaac Ghebre-Sellassie

Evaluation of acrylic-based modified-release film coatings

Abstract Although insoluble pharmaceutical additives have been generally incorporated into film-coating formulations to impart a particular color to a solid dosage form or to reduce tackiness during the coating process, the inclusion of insoluble excipients in Eudragit E 30 D formulations, instead of the commonly used hydrophilic polymers, generated predictable modified-release reservoir systems. Dissolution studies of Eudragit E 30 D-coated pellets indicated that the release profiles depended not only on the physicochemical properties of the drug, particularly solubility, but also on the coating levels and the ratio of the additive to Eudragit resin in the dry film. Moreover, the integrity of the coating material and hence the release rates were found to be independent of the pH of the dissolution medium. Storing the coated pellets below the softening temperature of the Eudragit film for an extended period of time did not lead to a significant change in the release profiles. The predominant mechanism of drug release appears to be diffusion through water-filled pores in the film coat. The pellets were overcoated with a water-soluble hydrophilic polymer to prevent aggregation and enhance flowability. The overcoat did not affect the rate or extent of drug release.

Application of Poly(oxyethylene) Homopolymers in Sustained Release Solid Formulations

AbstractWater soluble poly(oxyethylene) homopolymers, with molecular mass ranging from four hundred thousand to four million, were used as carriers to generate, by direct compression techniques, sustained release matrix tablets of both water-soluble and insoluble bioactive agents. Dissolution studies showed that the release kinetics of the tablets depends upon the solubility and molecular mass of polymer, solubility of drug, and the ratio of the drug to polymer in the tablets. Following drug release, the tablet components dissolved leaving behind no residue, or “ghost”, as is commonly observed with wax-based systems.

Evaluation of A High-Speed Pelletization Process and Equipment

AbstractA single step high-speed centrifugal pelletization procedure is described. Pellets of three model drugs of varying solubilities were prepared and characterized. Scanning electron microscopy showed that the external layer which is composed of binder and drug is very porous relative to the nonpareil seed core material. Bulk density measurements also confirmed the loose structural makeup of the drug layer. Preparation of pellets from small non-pareil seeds provided particles that have high drug content and are amenable to high dose formulations. Common wet granulation binders such as polyvinylpyrrolidone, sodium carboxymethylcellulose and gelatin exhibited good binding capacities and generated excellent pellets.

Preparation of microspheres of water-soluble pharmaceuticals

An emulsion-solvent evaporation procedure involving the dispersion of an alcoholic solution of an active in liquid paraffin was used to prepare microspheres of water-soluble pharmaceuticals using ethylcellulose as a carrier. The effects of surfactant, plasticizer, drug loading, and agitation speed on drug release rate from the microspheres were evaluated. The release rates of water-soluble drugs from microspheres, ranging from 100 and 500 microns in diameter, were sustained over an extended time and were found to be related to the ratio of drug to polymer in the final product.

The effect of product bed temperature on the microstructure of aquacoat-based controlled-release coatings

Abstract Diphenhydramine HCl pellets were coated at various bed temperatures in a laboratory-size fluid-bed equipment. Optimum coalescence of an Aquacoat formulation was achieved when the bed temperature was kept between 30 and 40°C. Coating applied outside this temperature range resulted in the formation of poorly coalesced films and faster release rates. The fast release rates of pellets coated at low bed temperatures were attributed primarily to drug migration into the film layer during the coating process and to incomplete film formation due to hardening of the uncoalesced polymer spheres, which, presumably, had a relatively higher minimum film formation temperature. At high bed temperatures, the rate of evaporation of water is so fast that it does not allow the migration of drug from the substrate into the film layer. The fast release rates observed were, therefore, believed to be due to the development of porous films during the coating process.

A unique application and characterization of Eudragit E 30 D film coatings in sustained release formulations

Abstract Eudragit is an aqueous dispersion of an acrylic resin that is based on poly(ethylacrylate-methylmethacrylate) esters. The polymer is neutral in character and hence is not sensitive to differences in pH. Incorporation of insoluble pharmaceutical additives in Eudragit E 30 D coating formulations instead of the commonly used hydrophilic polymers generated not only programmable sustained release reservoir systems but also protective coatings that are relatively resistant to water vapor permeation. The additives, such as kaolin and talc which are used as received without any pretreatment, exist as discrete particles within the polymeric matrix. Although they are not dispersed at the molecular level as are hydrophilic polymers, the insoluble solids are mixed uniformly within the polymeric dispersion to provide a homogeneous coat. The homogeneity of the coating material was confirmed both by dissolution studies and a microanalydcal technique that utilizes an energy dispersive X-ray spectrometer. In addition, scanning electron microscopic examination of the surface morphology of coated pellets that released their contents during dissolution and those which were not subjected to dissolution indicated that the physical adsorption of the insoluble additive in the polymeric matrix is permanent. These properties ensure both short- and long-term stability of the coating material and reproducible in vitro and in vivo release profiles.

The effect of spray mode and chamber geometry of fluid-bed coating equipment and other parameters on an aqueous-based ethylcellulose coating

Abstract Propranolol HCl pellets were prepared in a rotor-granulator by layering the drug powder onto nonpareil seeds. They were then coated with Aquacoat® (an aqueous dispersion of ethylcellulose) in fluid bed coating machines, i.e., Aeromatic Strea I or Glatt GPCG-1, using different spray modes and/or chamber geometries. Dissolution data and morphology studies of coated pellets indicated differences in the nature of the coatings. This phenomenon may be attributed to differences in the particle motion in the bed, particle distribution and density in the coating zone, as well as the direction and the distance the sprayed droplets traverse prior to impinging on the particles. In addition, bed load and substrate frriability also appeared to affect the deposition of coating. Therefore, it is essential that for controlled-release coatings, the optimization of the fluid bed process be preceded by a careful evaluation of the spray mode and chamber geometry for a given piece of equipment.

Manufacture and Properties of Erythromycin Beads Containing Neutron-Activated Erbium-171

To evaluate the effects of a neutron activation radiolabeling technique on an enteric-coated multiparticulate formulation of erythromycin, test quantities were produced under industrial pilot scale conditions. The pellets contained the stable isotope erbium oxide (Er-170), which was later converted by neutron activation into the short-lived gamma ray-emitting radionuclide, erbium-171. In vitro studies indicated that the dissolution profile, acid resistance, and enteric-coated surface of the pellets were minimally affected by the irradiation procedure. Antimicrobial potency was also unaffected, as determined by microbiological assay. Neutron activation thus appears to simplify the radiolabeling of complex pharmaceutical dosage forms for in vivo study by external gamma scintigraphy.

Effect of the crystallization process and solid state storage on the physico-chemical properties of scale-up lots of CI-936

AbstractN-(2,2-diphenylethyl)adenosine, designated as CI-936, is a novel, orally active antipsychotic agent. Depending on the manufacturing process, the drug substance exists in more than one crystalline form. Three lots of the drug were characterized by thermal analysis, scanning electron microscopy, X-ray diffraction, and dissolution. Two of these lots were found to be crystalline while the third was amorphous. The physical properties of the crystalline forms appear to change during storage under ambient conditions. The amorphous form, inspite of being in a high energy state, was not affected by storage. The absolute bioavailability of the amorphous form in dogs is more than 90%. In contrast, the other two crystalline lots demonstrated lower and unpredictable oral absorption profiles.