Biomedical subjects

E Galia

Publications and source records attributed to E Galia.

4 recordsLinked to original sources

PubMed1999

Albendazole generics--a comparative in vitro study.

PURPOSE: We sought to determine whether disintegration and dissolution behavior differs among various albendazole generic formulations obtained from third world countries and to compare them with the innovator's product. METHODS: Dissolution behavior of various albendazole formulations was studied with USP Apparatus 2 in SGFsp and in a modified SGFsp which contained 0.1% of the nonionic surfactant Triton X 100. Disintegration was tested according to the European Pharmacopoeia. RESULTS: Dissolution experiments in SGFsp showed a wide range in rate and extent of albendazole dissolution. The innovator product released 81 percent within two hours, a profile matched by only one other formulation. For other formulations 32 to 64% was released within two hours. Use of a modified SGFsp, containing 0.1% Triton X 100 to simulate the surface tension of gastric juice, resulted in less discrimination between products. The innovator product again showed the fastest and most complete dissolution, with ninety percent released within two hours. The generic formulations released between 67 and 82%, except for one formulation which achieved only 43% release. The results in SGFsp plus Triton X 100 may be more meaningful than in SGFsp since the surface tension of the medium is closer to the physiological value. All formulations passed the disintegration test according to the European Pharmacopoeia, with disintegration times ranging from 2.5 to 11 minutes. CONCLUSIONS: Generic albendazole products vary widely in their dissolution behavior. Differences among products were greater in SGFsp than in SGFsp plus Triton X 100. These differences were not reflected in the disintegration behavior of the products.

Albendazole↗

PubMed1999

Forecasting the in vivo performance of four low solubility drugs from their in vitro dissolution data.

PURPOSE: To assess the usefulness of biorelevant dissolution tests in predicting food and formulation effects on the absorption of four poorly soluble, lipophilic drugs. METHODS. Dissolution was studied with USP Apparatus II in water, milk, SIFsp, FaSSIF, and FeSSIF. The in vitro dissolution data were compared on a rank order basis with existing in vivo data for the tested products under fasted and fed state conditions. RESULTS: All drugs/formulations showed more complete dissolution in bile salt/lecithin containing media and in milk than in water and SIFsp (USP 23). Comparisons of the in vitro dissolution data in biorelevant media with in vivo data showed that in all cases it was possible to forecast food effects and differences in absorption between products of the same drug with the physiologically relevant media (FaSSIF, FeSSIF and milk). Differences between products (both in vitro or in vivo) were less pronounced than differences due to media composition (in vitro) or dosing conditions (in vivo). CONCLUSIONS: Although biorelevant dissolution tests still have issues which will require further refinement, they offer a promising in vitro tool for forecasting the in vivo performance of poorly soluble drugs.

Adamantane↗

PubMed1998

Evaluation of various dissolution media for predicting in vivo performance of class I and II drugs.

PURPOSE: In this paper we seek to verify the differences in dissolution behavior between class I and class II drugs and to evaluate the suitability of two new physiologically based media, of Simulated Gastric Fluid (SGF) and of milk for their ability to forecast trends in the in vivo performance of class II compounds and their formulations. METHODS: Dissolution behavior of two class I drugs, i.e. acetaminophen and metoprolol, and of three class II drugs, i.e. danazol, mefenamic acid and ketoconazole, was studied with USP Apparatus 2 in water, SGF, milk, Simulated Intestinal Fluid without pancreatin (SIFsp) and in two media simulating the small intestinal contents in the fed (FeSSIF) and fasted (FaSSIF) states, respectively. RESULTS: Class I powders dissolved rapidly in all media tested. Acetaminophen dissolution in milk was slow from one tablet formulation, in all other cases dissolution was more than 85% complete in 15 minutes. The dissolution rate of metoprolol was shown to be dependent on formulation and manufacturing method, and one of the three tablet formulations did not meet compendial specifications (80%/30 minutes). Dissolution behavior of class II drugs was greatly affected by choice of medium. Dissolution from a capsule formulation of danazol proved to be dependent on the concentration of solubilizing agents, with a the 30-fold increase in percentage dissolved within 90 minutes upon changing from aqueous media without surfactants to FaSSIF. Use of FeSSIF or milk as the dissolution medium resulted in an even greater increase in percentage dissolved, 100 and 180-fold respectively. Dissolution of the weak acid mefenamic acid from a capsule formulation is dependent on both pH and bile salt concentration, which leads to an offset between increased bile salt concentration and lower pH in the fed state compared to the fasted state medium. The weak base ketoconazole showed complete dissolution from a tablet formulation in Simulated Gastric Fluid without pepsin (SGFsp) within 30 minutes, 70% dissolution in 2 hours under fed state simulated upper jejunal conditions but only 6% dissolution in 2 hours under fasted state conditions. CONCLUSIONS: As predicted, dissolution of class II drugs proved to be in general much more dependent on the medium than class I drugs. With the array of compendial and physiological media available, it should be possible to design a suitable set of tests to predict the in vivo dissolution of both class I and II drugs from immediate release formulations.

Acetaminophen↗

PubMed1995

Pharmacokinetic and pharmacodynamic evaluation of triamcinolone acetonide after intravenous, oral, and inhaled administration.

Triamcinolone acetonide (TCA) is a corticosteroid that is frequently used in the treatment of asthma. After inhalation, TCA can become systemically available when the inhaled formulation is swallowed, causing undesirable systemic effects. A clinical study was conducted to determine the systemic side effects of TCA after intravenous (2 mg as phosphate ester), oral (5 mg), and inhaled (2 mg) administration. Blood samples were collected at appropriate times over 24 hours, and TCA concentrations in plasma were measured by high-performance liquid chromatography and radioimmunoassay. Free drug concentrations were determined by ultrafiltration for correlating pharmacokinetics and pharmacodynamics. The free fraction of TCA (+/- standard deviation) was 29.0 +/- 1.3% and was independent of the investigated concentration range up to 1,000 ng/mL. Pharmacodynamic parameters were determined by monitoring lymphocytes, granulocytes, and cortisol. Pharmacokinetic/pharmacodynamic modeling was performed using a modified Emax model for lymphocytes and granulocytes. A novel linear release rate model was used to characterize the cortisol data. The E50 values determined from all three pharmacodynamic endpoints were not significantly different for the three treatments, indicating that these effects can be explained based on systemic steroid concentrations.

Administration, Inhalation↗