Charles I. Jarowski

Powdered solution technology: principles and mechanism.

The concept of powdered solutions can be used to formulate liquid medications in dry, nonadherent, free-flowing, and readily compressible powders. The technique is based on simple admixture of drug solution or liquid drug with selected carrier and coating materials. Improved drug release profiles are exhibited by such delivery systems even for poorly water-soluble drugs. Previous work using this method has rendered its industrial application impractical because of the unsatisfactory flow properties of the powder admixtures. This article presents a theoretical model based on the principles and mechanism of powdered solutions and introduces a new physical property of powders termed the flowable liquid-retention potential (Φ value). Mathematical expressions are derived that can be used to calculate the optimum amount of excipients required to yield powder admixtures with acceptable flowability. The validity and applicability of these expressions have been verified experimentally using clofibrate and prednisolone as test materials. The proposed model is shown to be superior to previously reported studies in optimizing the amount of excipients needed to prepare powdered solutions with acceptable flow properties.

Use of Powdered Solutions to Improve The Dissolution Rate of Polythiazide Tablets

AbstractSolutions of polythiazide in polyethylene glycol 400 were admixed with microcrystalline cellulose (RC-591) and silica. The resulting free-flowing powder was incorporated into tablet formulations by direct compression.The dissolution rates of polythizizde frm these tablets were significantly more rapid than from commercially available tablets. The stability of these tablets at 40°0C and high humidity was studied. The powdered solution formulas were also compared with a polythiazide dispersion in polyethylene glycol 6000 which exhibited an equally superior dissolution profile.

Effect of lysine on toxicity and depressant effects of ethanol in rats

Abstract When l -lysine was administered prior to toxic doses of ethanol, the LD50 for ethanol was slightly increased after both po and ip administration. The onset of ethanol-induced sleeping time was prolonged while the duration was reduced by pretreatment with l -lysine.

Effect of tryptophan on toxicity and depressant effects of barbiturates and ethanol in rats

When the fasting plasma amino acid profile of Sprague-Dawley rats was determined chromatographically, it was found that, of the essential amino acids, 1-tryptophan and 1-methionine were present in the lowest concentration. Using 1-tryptophan because of its reported antidepressant effects, it was found that pretreatment of rats with this amino acid decreased the LD50 and prolonged the sleeping times and immobility times previously determined for pentobarbital, hexobarbital, and ethanol. It is concluded that acute administration of 1-tryptophan will not reverse the toxicity of these CNS depressants.

The Dissolution Hate and the Ohal Absorption Eficificy of Selected Salicylates from Lipid Drug Delivery Systers

Abstractp-Sitosterol, cholesterol and its acetate and n-aecylate esters were used. in 3, 4.5 and 6-fola excess with salicylic acia, salicylamide, aspirin and metnyl sallcylate with and without lactsse. Dissolution stuaies were conaucted in simulatea gastrointestinal fluios with and without sodium cnolate. Tne in vitro aissolution rate of salicylic &c10 was markedly enhanced in the presence of the Dile salt. Although the aissolution rates of the salicylates from the lipid systems were significantly reduced, the rate and extent of appearance of salicylate in the urine of two test subjects were similar to plain salicylic acia. The urine recovery of free salicylate seemed to be increased when the lipid vehicle was cholesteryl n-becylate.

Effect of Granulating Method on Content Uniformity and Other Physical Properties of Granules and their Corresponding Tablets. II

AbstractVarious properties of dexamethasone and sulfadiazine granules and tablets prepared by microgranulation, slugging, wet granulation and direct compression were compared.The dexamethasone tablets showed comparable disintegration rates by all methods. The sulfadiazine tablets prepared by slugging did not meet the USP XIX limit, whereas those by microgranulating were satisfactory.It was found that granule-homogeneity was not only dependent on the particle size and distribution, but also dependent on the granulating method. For either drug, the microgranulating procedure gave the best weight and content uniformity.

Effect of Granulating Method on Particle Size Distribution of Granules and Disintegrated Tablets. I

AbstractThe average particle size and distribution of granules were found to be dependent on the granulating method. The slugging method produced the widest particle size distribution and the largest average particle size, while the microgranulating method produced the narrowest distribution and the smallest average particle size. The average particle size of dexamethasone granules produced by wet granulating, microgranulating and slugging methods, were reduced on compaction by fragmentation. Of the three, the granules prepared by the slugging method, exhibited maximal average size reduction on compaction. On the other hand, the average particle size of sulfadiazine microgranulates and sulfadiazine slugs were enlarged by consolidation during compaction.

Dissolution Rates of Prednisolone Triturations Using Porous and Non-Porous Silicas. I. Pilot Oral Absorption Study in Dogs

AbstractPrednisolonei:Silica triturations were prepared with 5 grades of silicas by ball-milling and solvent deposition. Drug:Silica ratios ranged from 1:0.11 to 1:19. Dissolution rates in simulated intestinal juice were greatest for the l:0.11 triturations prepared by solvent-deposition. Oral absorption efficiency of prednisolone in dogs was similar whether administered as porous or non-porous silica triturations.

Effect of Granulating Method on Dissolution Rate of Compressed Tablets. III

AbstractThe dissolution rates of dexamethasone granules prepared by all the methods were slower than the dissolution rates of the corresponding tablets. This was shown to be the result of a reduction of the average particle size on compaction. The dissolution rates of sulfadiazine tablets prepared by microgranulating and slugging were slower than the corresponding granules. This was demonstrated to be the result of enlargement of the granules on compaction. For both drugs the microgranulating procedure gave the most rapid dissolution of tablets and granules. In case of the dexamethasone formulation, direct compression exhibited the slowest dissolution rate. The dissolution rates of sulfadiazine granules and tablets prepared by the wet granulating method were also unsatisfactory.