Leah Elizabeth Appel

Use of Modified Ethylcellulose Lattices for Microporous Coating of Osmotic Tablets

Commercially available lattices are often used to coat nonpareils or beads. Drug release occurs via diffusion through the polymer coating. Adequate release rates may be achieved with small particles because the surface area is large. However, tablets coated with unmodified lattices have exceedingly slow release rates. Therefore, a pore-forming agent, urea, was added to a commercially available ethyl cellulose latex, Aquacoat, to increase the release rate of drugs from coated osmotic tablets. Modified lattices were used to coat KC1 and diltiazem · HC1 tablets. Release of KC1 and diltiazem into water or buffer solutions was determined in a standard U.S.P. dissolution apparatus. Rates varying from 1 to 100% release in 12 hr were obtained by varying the coating thickness, pore-former level, and plasticizer type and concentration. Scanning electron microscopy (SEM) showed that the urea was eluted from the coat in aqueous solution leaving a porous coating. Coat burst strengths were dependent on the coat thickness and the concentrations of pore former and plasticizer. Hence, modified lattices hold potential for use as coatings for controlled release osmotic formulations.

Relationship Between Drug Absorption Enhancing Activity and Membrane Perturbing Effects of Acylcarnitines

Acylcarnitines with chain lengths of 2 to 18 carbon atoms were tested for their effects on rat intestinal brush border membrane order (S) by fluorescence polarization of 1,6-diphenyl-l ,3,5-hexatriene (DPH). These results were compared to the previously reported effectiveness of the acylcarnitines as absorption enhancers of the poorly absorbed antibiotic cefoxitin. Acylcarnitines with fatty acids less than 12 carbon units in length were ineffective in increasing drug absorption and perturbing brush border membrane order. Long-chain acylcarnitines (12–18 carbons) significantly increased the bioavailability of cefoxitin and decreased the lipid order of brush border membranes. The results suggest that, in order to promote drug absorption, the acylcarnitines must surpass a critical chain length (10 carbon units) to partition effectively into the membrane and, in addition, must perturb the lipid order beyond a threshold value (15–20%). Membrane perturbing capacity may serve as an indicator of the absorption enhancing potential of other aliphatic-type compounds.

Formulation and optimization of a modified microporous cellulose acetate latex coating for osmotic pumps.

A cellulose acetate (CA) latex was modified for use as a microporous coating for osmotic devices. Potassium chloride core tablets were coated with a CA latex formulation containing a plasticizer (triacetin) and a pore-forming agent (urea). To promote the coalescence of the cellulose acetate latex beads into a film on the surface of the tablet, it was necessary to cure the coated tablets, hereafter referred to as devices, at elevated temperatures. The objectives were to determine the effect of four formulation variables (plasticizer level, pore former level, cure time, and cure temperature) on the in vitro KCl release rate and coat burst strength using a full 24 factorial experimental design. Burst strength was measured as the number of grams force a depleted device could support before bursting. The results indicated that urea content was the most important variable, followed by triacetin content and cure time. Cure temperature did not influence the results. Response surfaces generated with the experimental values were used to predict a formulation which would have both a high release rate and a high burst strength. This formulation was prepared and tested both in vitro and in vivo in dogs. The in vitro release rate and burst strength results agreed with those predicted by the model. The in vitro and in vivo release rates were not statistically significantly different as determined by ALQ analysis.

In vitro characterization and in vivo efficacy of a prostaglandin E2/poly(ortho ester) implant for bone growth promotion

Abstract Prostaglandin E 2 (PGE 2 ) is a known stimulator of bone growth, yet when systemically administered at efficacious levels there are serious side effects. It was hypothesized that local delivery of a low dose of PGE 2 would increase the rate of bone growth without systemic side effects. Biodegradable poly (ortho ester) (P (OE)) implants (4 mg, diameter = 2 mm, heights 1 mm) containing three different loadings of PGE 2 (0.81, 0.035 or 0.0032% PGE 2 w/w) were fabricated, characterized for in vitro release, and implanted in vivo in rat tibiae for 8 days. The PGE 2 release rate in vitro increased with increased initial loading of PGE 2 ; this increase was faster than predicted by a diffusional matrix release mechanism and was consistent with acid catalyzed P(OE) degradation in response to the PGE 2 . In vivo, bone was examined at the end of the 8 day implantation period for new growth. These studies showed that the implants with the two highest loadings significantly enhanced (up to 3-fold) localized bone growth with no observable side effects in any of the treatment groups. This approach may be useful for enhancing bone growth in clinical situations which require bone augmentation or repair.

Oncologic, Endocrine & Metabolic Overview: Recent advances in implants for bone growth promotion

Devices intended for delivery of bone growth promoters should possess several properties. The device should have enough strength to hold the bone in place during the course of fixation, yet it should be biodegradable so that ultimately replacement by new bone will occur. This requires that the device has a certain level of porosity to allow for the ingrowth of new bone during the healing process. Many materials can be utilised for implants including naturally occurring materials (e.g., bone, fibrin, collagen) and synthetic materials (polymers, ceramics, metals). The appropriate material should be biocom-patible and not inhibit bone growth. Many approaches combining various active agents (e.g., bone morphogenic proteins, transforming growth factor, prostaglandins) with one of several synthetic or naturally occurring matrices have been examined. Several systems show promising initial results; however, the actual bone growth promoter release profiles required for efficacious treatment have not yet been estab...