Effect of glycine/citric acid on the dissolution stability of hard gelatin capsules.

Gelatin capsule crosslinking is a well-known phenomenon that results in reduced dissolution of capsule products with the passage of time and/or under accelerated stability conditions. These studies describe one means of preventing capsule crosslinking by incorporating glycine and citric acid into a triamterene/hydrochlorothiazide 37.5/25 mg capsule formulation (triam/HCTZ). Triam/HCTZ without glycine and citric acid showed extensive capsule crosslinking and then failed the USP dissolution specification after a 4-week accelerated (40 degrees C/85% relative humidity [RH]) stability study. Triam/HCTZ containing glycine alone showed some improvement in the dissolution stability but did not prevent gelatin crosslinking. This formulation also failed dissolution specifications after a 4-week accelerated stability study. The same results were obtained when only citric acid was incorporated into the triam/HCTZ. However when glycine and citric acid were incorporated together into the triam/HCTZ, crosslinking was completely prevented. Dissolution profiles remained the same throughout 12-week accelerated stability studies, with little or no drop in the dissolution values throughout the test period. The above results were confirmed with follow-up studies using gemfibrozil and piroxicam as model drugs. Disintegration times for gemfibrozil and piroxicam capsule formulations without glycine and citric acid increased dramatically with observed pellicle formation, but there was little or no change in the disintegration time of the model drugs formulated with glycine and citric acid. The results of these studies demonstrated that when glycine and citric acid are present in some gelatin capsule formulations, pellicle formation or crosslinking of the capsule gelatin is prevented.

Compounding times and contamination rates associated with the preparation of intravenous admixtures in three types of plastic containers.

The compounding times and contamination rates associated with the preparation of admixtures in three different plastic i.v. containers of dextrose 5% in water were compared. The time required for a technician to prepare, in a laminar air flow hood by the needle and syringe technique, 120 admixtures in each of three different plastic i.v. containers was measured and recorded by two investigators. The 360 admixtures were tested within one hour of preparation for sterility using an enriched brain heart infusion broth. The total time required to compound the i.v. admixtures varied significantly with container design (p less than 0.01), preparation being fastest with the Accumed container, followed by the LifeCare then the Viaflex containers. The major contributing factors to increased compounding time were (1) removal of outer wrap, (2) swabbing of LifeCare and Viaflex medication ports with isopropyl alcohol pads and (3) freeing of the hangar flap from the Viaflex container. Sterility tests revealed no detectable contamination of any of the admixtures. Container design of plastic i.v. containers did influence the preparation time for admixtures but did not influence admixture sterility.

Stability of nitroglycerin injection determined by gas chromatography.

The stability of nitroglycerin injection was studied over an eight-week period. Gas-liquid chromatographic assay and thin-layer chromatography were used to study the stability in relation to sorption by rubber and plastic (Viaflex), light and the effect of two diluents (5% dextrose in water and 0.9% sodium chloride for injection). More nitroglycerin was lost from vials with rubber closures, and the loss occurred at a faster rate when compared with nitroglycerin packaged in ampuls. There was no difference in the loss of nitroglycerin from injection packaged in ampuls when stored in the light or in the dark, or in the loss of nitroglycerin from two diluents, 5% dextrose in water and 0.9% sodium chloride for injection, packaged in glass bottles. A 70.4% greater loss of nitroglycerin occurred from Viaflex bags than from glass bottles. Loss of nitroglycerin in this study may have been characterized by reversible first-order kinetics.