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Biomedical subjects

C I Jarowski

Publications and source records attributed to C I Jarowski.

At least 19 recordsLinked to original sources
PubMed1993

Influence of pH on release of phenytoin sodium from slow-release dosage forms.

Physicochemical factors influencing the release of phenytoin sodium from slow-release dosage forms were studied. Some of these factors were solubility and intrinsic dissolution rate as functions of pH, type of dosage form, pH of dissolution medium used, and conversion of the sodium salt to free acid (phenytoin). The innovator's product, Extended Phenytoin Sodium Capsule (Dilantin Kapseal, 100 mg, Parke-Davis), and two experimental formulations (one nondisintegrating tablet containing polymeric materials and the other a solid dispersion in an erodible matrix) served as the slow-release dosage forms. The sodium salt converts to practically insoluble phenytoin in the gastrointestinal pH range of 1 to 8. Due to such a conversion inside or at the surface of slow-release dosage forms, the release of drug in this pH range was incomplete. The extent of drug release also varied with the type of formulation used. In contrast, complete dissolution could be obtained in water because the pH of the medium gradually rose from approximately 6 to approximately 9.2 where the drug solubility was higher. Although several phenytoin sodium products might have similar dissolution rates in water, the extents of drug release under gastrointestinal pH conditions (pH 1-8) could differ greatly, thus supporting the Food and Drug Administration recognition that the similarity in dissolution profiles in water does not assure that the products are bioequivalent. The reported lower steady-state level of phenytoin in human plasma following oral administration of a slow-release dosage form may be related to incomplete drug release.

Chemistry, Pharmaceutical↗
PubMed1992

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 (phi 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.

Chemical Phenomena↗
PubMed1991

Instability of digoxin in digoxin-amorphous silicon dioxide triturates prepared by solvent deposition and ball milling.

Digoxin underwent hydrolytic degradation to its molecular components when solvent deposited on or ball milled with various commercial grades of amorphous silicon dioxide. The degradation was greater during ball milling than after solvent deposition, and increased with a longer ball milling. By itself digoxin was also degraded by ball milling, but not as much as when a silicon dioxide was present. The extent of the degradation appeared to depend on the acidity, surface area and pore size of the silicon dioxide used. A similar degradative behavior was observed for the related glycoside digitoxin.

Chemistry, Pharmaceutical↗
PubMed1985

Effect of diffusion layer pH and solubility on the dissolution rate of pharmaceutical bases and their hydrochloride salts. I: Phenazopyridine.

The pH-solubility profile of phenazopyridine as determined by the addition of HCl or NaOH solutions to its aqueous suspension was identical to that of its hydrochloride salt except during phase transition from base to salt. With the addition of HCl to a suspension of the base, the pH dropped to a certain point and then remained constant until a supersaturated solution was formed. Only after a high supersaturation did precipitation of the hydrochloride salt occur. The solubility of the salt decreased at low pH due to a common ion effect. Unlike solubility profiles, the pH-intrinsic dissolution rate profiles of the base and its salt differed greatly. At low pH, the dissolution rate of the hydrochloride salt decreased with an increase in HCl concentration, whereas the dissolution rate of the base increased. The self-buffering action of the base and the increase in solubility, leading to a supersaturation of the diffusion layer was responsible for the increase in its dissolution rate with a lowering of the pH of the medium. Good conformity with the Noyes-Whitney equation was demonstrated when the solubility values under pH conditions such that the diffusion layer thickness approaches zero (Cs,h = 0) were used rather than solubilities under pH conditions of the bulk media (Cs). Supersaturation of the dissolution medium was observed during dissolution of the hydrochloride salt at pH 7.

Aminopyridines↗
PubMed1985

Effect of diffusion layer pH and solubility on the dissolution rate of pharmaceutical acids and their sodium salts. II: Salicylic acid, theophylline, and benzoic acid.

The pH-solubility profiles of salicylic acid and theophylline, as determined by the addition of HCl or NaOH to their aqueous suspensions, were identical with those of their sodium salts except during phase transitions from acid to salt or vice versa. Supersaturated solutions were formed during phase transitions. Unlike the solubility profiles, the pH-intrinsic dissolution rate profiles of an acid and its salt differed greatly. Good conformity with the Noyes-Whitney equation was demonstrated when the solubility values under pH conditions as the diffusion layer thickness, h, approaches zero (Cs,h = 0) were used rather than solubilities under pH conditions of the bulk media (Cs). The pH when h approaches zero (pHh = 0) was estimated by equilibration of a dissolution medium with an excess of material. Good correlation was shown between the pHh = 0 values of benzoic acid estimated according to this method and the pHh = 0 values reported in the literature. The intrinsic dissolution rate constant, the ratio of the diffusion coefficient to the diffusion layer thickness (D/h), may be assumed constant when comparing the dissolution rates of salicylic acid, theophylline and sodium theophylline. On the other hand, D/h decreased significantly during dissolution of sodium salicylate due to a large increase in Cs,h = 0 and the consequent increase in viscosity in the diffusion layer. A simple method of predicting the dissolution rate of an acid or a salt at different pH values has been developed.

Acids↗
PubMed1984

Dissolution rates of corticoid solutions dispersed on silicas.

Two nonporous and three porous amorphous silicas were used as dispersion media to convert corticoid solutions into free-flowing powders. The corticoids (prednisone, prednisolone, and hydrocortisone) were dissolved in N,N-dimethylacetamide-polyethylene glycol 400 (7:3 v/v) and their 10% (w/v) solutions were mixed with the silicas (1:3 v/w). Dissolution rates of the corticoids from such powdered solutions were more rapid than their micronized powders in various aqueous media.

Adrenal Cortex Hormones↗
PubMed1983

Solid dispersions of testosterone with reduced presystemic inactivation.

Dissolution rates of solid dispersions of testosterone in various lipids or polyethylene glycol 6000 with and without surfactants were determined. In a limited study, selected dispersions were evaluated for oral absorption efficiency in a 32-year-old male. Significant reductions in urinary testosterone metabolites to testosterone ratios were observed with a 1:4 weight ratio of testosterone-polyethylene glycol 6000 and a 1:4:0.25 weight ratio of testosterone-cholesteryl stearate-sorbitan monolaurate.

Adult↗
PubMed1983

Stabilizing effect of fructose on aqueous solutions of hydrocortisone.

Accelerated stability studies (37 degrees, 47 degrees, and 57 degrees) were conducted on buffered aqueous solutions (pH 7.4, 8.4, and 9.4) of hydrocortisone in the presence of various molar ratios of D-fructose. First-order degradation was observed. Significant improvement in hydrocortisone stability was seen in those solutions containing a 25 M excess of D-fructose. Hydrocortisone solutions containing dextrose, lactose, sucrose, sorbitol, propylene glycol, or glycerin in the same molar ratio were not stabilized.

Drug Stability↗
PubMed1982

Leukemic infiltration of the cerebellum in acute myelomonocytic leukemia.

A 31-year-old woman with acute myelomonocytic leukemia presented with meningeal signs and a cerebellar mass attributed to leukemic infiltration. The mass disappeared with radiation therapy and intraventricular chemotherapy, but the patient subsequently suffered several spinal nerve root recurrences, disseminated herpes zoster, and progressive multifocal leukoencephalopathy. At autopsy, there was no trace of the meningeal leukemia or cerebellar infiltrate. This case illustrates several of the neurologic complications of acute nonlymphocytic leukemia, and raises the question whether patients with the myelomonocytic form of this disease might benefit from prophylactic central nervous system treatment.

Adult↗
PubMed1981

Modified colorimetric method of plasma prednisolone.

A simple, precise, rapid, and sensitive colorimetric method was adapted for the quantitative analysis of prednisolone in dog plasma. A paper chromatographic procedure was modified by the use of thin-layer plates coated with microcrystalline cellulose. Heparinized blood samples were separated from the cellular elements and extracted with methylene chloride. After washing with acid and alkali, the extract was evaporated to dryness. The residue was dissolved in methanol and streaked on the TLC plate. After development, the band that was detected by UV light was scraped off and extracted with methanol. The methanol extract was treated with the Porter-Silber reagent (phenylhydrazine). Absorbance was measured at 410 nm. Replicate assays indicated a mean recovery of 97.5% and a coefficient of variation of 5.13%.

Animals↗
PubMed1980

Disseminated candidiasis. Newer approaches to early recognition and treatment.

The clinical triad of fever, erythematous papular rash, and diffuse muscle tenderness has recently been reported to be presumptive evidence for disseminated candidiasis in the immunocompromised host who is receiving broad-spectrum antibiotics. This case report further explores this clinical association and demonstrates that the immediate institution of antifungal therapy before laboratory test results are known may favorably alter the outcome of this frequently fatal condition. In view of the low positive yield of blood cultures, skin biopsy may represent an effective method for achieving rapid laboratory confirmation of the diagnosis.

Adult↗
PubMed1980

Solid dispersion of morphine-tristearin with reduced presystemic inactivation in rats.

Solid dispersions of morphine in tristearin, beta-sitosterol, and cholesterol were prepared by evaporation of their ethanol solutions. Weight ratios of morphine-lipid of 1:1, 1:3, and 1:4.5 were prepared. Dissolution studies of the solid dispersions and morphine were conducted in a simulated GI medium at 37 degrees. The release rates of morphine from the tristearin dispersions were the slowest. The 1:1 morphine-tristearin dispersion was administered orally to rats. Free and total morphine levels in rat urine were determined by spectrofluorometric and enzymatic immunoassay procedures, respectively. The morphine-tristearin dispersion yielded a higher percentage of free morphine after 24 and 48 hr as compared with morphine and its sulfate.

Animals↗
PubMed1980

Lowering of serum cholesterol and triglyceride levels by balancing amino acid intake in the white rat.

Earlier studies in rats have shown that serum cholesterol levels were significantly lower in rats fed an L-lysine-supplemented ration. This investigation was initiated to determine if the reverse was true. We reasoned that the addition of an incomplete protein to a complete rat ration would bring about an increase in serum lipid levels. This would result from the intermediary metabolic conversion of systemic amin acids not used in protein synthesis. We further postulated that supplementation of the imbalanced protein would obviate the hyperlipidemia. Gelatin was chosen as the incomplete protein since it is deficient in tryptophan, an essential amino acid. Adult male Sprague-Dawley rats fed rations with added gelatin (5, 15 and 25%) for 30 days showed significant increases in serum cholesterol and triglyceride levels. Lipid levels in rats fed L-tryptophan-supplemented diets containing the same levels of gelatin did not differ from those animals fed the control ration. The data indicate that hyperlipidemia results from the feeding of imbalanced protein. Such hyperlipidemia can be obviated by supplementation with the limiting amino acid.

Amino Acids↗
PubMed1979

Hepatic Hodgkin's disease without involvement of the spleen.

A patient with Hodgkin's disease, who at laparotomy had liver involvement with no evidence of Hodgkin's disease in the spleen, is reported. Rare alternate lymphaticovenous anastomoses exist that may lead to liver involvement in the absence of splenic involvement.

Aged↗
PubMed1979

Effects of amorphous silicon dioxides on drug dissolution.

The dissolution profiles of prednisone, digoxin, and griseofulvin in simulated GI fluids were determined after solvent deposition or ball milling with three commercially available grades of amorphous silicon dioxide. The former procedure resulted in adsorbates showing evidence of drug entrapment by the two grades with larger average pore diameters. Ball milling the drugs with the grade possessing the largest average particle diameter produced triturations with the slowest dissolution rates. A relationship between drug dissolution and extent of dilution with the amorphous silicon dioxides was shown. Particle-size measurements revealed that the ball milling procedure was more apt to broaden the size distribution as compared with the solvent-deposition method of drug incorporation.

Chemistry, Pharmaceutical↗