Russell U. Nesbitt

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.

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.

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.

Stability Studies of Gabapentin in Aqueous Solutions

Gabapentin is a γ-aminobutyric acid analogue, which has been shown to be an effective antiepileptic. The solution stability of gabapentin in buffered systems was studied in order to facilitate the formulation of a liquid product. The degradation of the drug was followed as a function of pH, buffer concentration, ionic strength, and temperature. The results indicated that the rate of degradation was proportional to the buffer concentration and temperature. The pH–rate profile of gabapentin degradation showed that the rate of degradation was minimum at an approximate pH of 6.0. Further, the data suggested a slower solvent-catalyzed degradation rate for the zwitterionic species compared to the cationic or anionic species in the pH range of 4.5 to 7.0. There was no influence of ionic strength on the rate of degradation. Arrhenius plots of the data indicated that a shelf life of 2 years or more at room temperature may be obtained in an aqueous solution at a pH value of 6.0.

Effect of substrate on mass release from ethylcellulose latex coated pellets

Abstract The release of water soluble substrates from Aquacoat coated pellets was through water-filled channels. Each pellet works like a mini osmotic pump with many orifices (pores). The energy to drive the system was supplied by the osmotic pressure differences generated between the internal medium in the coated pellets and the external dissolution medium. The channels or pores were artifacts of the coating process and were not found in free films prepared from the coating dispersion. The free films were not permeable to the water soluble substrates, e.g., diphenhydramine HCl (D), pseudoephedrine hydrochloride (P) and FD&C red dye #40 (RD). However, the compounds were released easily from the coated DPRD pellets. The size and extent of channel production in the controlling membrane were directly related to the surface properties of the core pellets. Scanning electron microscopy and mercury porosimetry studies revealed that the coated sugar pellets (SRD) have more uniform channels of smaller diameter than the DPRD pellets. The surface of the DPRD core pellets is ionizable and more water soluble than the SRD core surface. The release rate from the pellets was dependent on the substrate solubility and the osmotic pressure of the external dissolution medium. The release rate from the coated pellets initially was zero order and changed to first-order when there was no solid substrate left in the pellets. The zero order portion of release was shorter for water soluble compounds ( 24 h for theophylline (T). The release rate of T was increased by incorporation of a more water soluble substrate, D, in the pellets.

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.

Characterization of Commercial Lots of Erythromycin Base

AbstractThe physical properties of five commercial lots of erythromycin base were evaluated with the object of characterizing the bulk chemical. The materials were investigated by thermal analyses, IR spectroscopy, Xray powder diffractions, equilibrium solubility in distilled water, and dissolution rates in phosphate buffer pH 7.5. Among the lots examined, three were found to be polymorphic variants of crystalline dihydrate, one a crystalline anhydrate and the other an amorphous solid. The different crystalline dihydrates displayed considerable variation in thermal properties but showed similar equilibrium solubilities in distilled water. At a given temperature, crystalline anhydrate has a higher aqueous solubility compared to the dihydrates. All crystalline forms of erythromycin showed rapid in vitro drug release from loosely-filled capsules. In contrast, the amorphous form exhibited a high equilibrium solubility but slower dissolution rate, a result attributable to its poor wettability. Contact angle me...