PubMed Health⌕ Search

Biomedical subjects

H O Ammar

Publications and source records attributed to H O Ammar.

At least 19 recordsLinked to original sources
PubMed2006

Design of a transdermal delivery system for aspirin as an antithrombotic drug.

Aspirin has become the gold standard to which newer antiplatelet drugs are compared for reducing risks of cardiovascular diseases, while keeping low cost. Oral aspirin has a repertoire of gastrointestinal side effects even at low doses and requires high frequent dosing because it undergoes extensive presystemic metabolism. Transdermal delivery offers an alternative route that bypasses the gut and may be more convenient and safer for aspirin delivery especially during long-term use. This study comprised formulation of aspirin in different topical bases. Release studies revealed that hydrocarbon gel allowed highest drug release. In vitro permeation studies revealed high drug permeation from hydrocarbon gel. Several chemical penetration enhancers were monitored for augmenting the permeation from this base. Combination of propylene glycol and alcohol showed maximum enhancing effect and, hence, was selected for biological investigation. The biological performance of the selected formulation was assessed by measuring the inhibition of platelet aggregation relevant to different dosage regimens aiming to minimize both drug dose and frequency of application. The results demonstrated the feasibility of successfully influencing platelet function and revealed that the drug therapeutic efficacy in transdermal delivery system is dose independent. Biological performance was re-assessed after storage and the results revealed stability and persistent therapeutic efficacy.

Administration, Cutaneous↗
PubMed2006

Implication of inclusion complexation of glimepiride in cyclodextrin-polymer systems on its dissolution, stability and therapeutic efficacy.

The effect of complexation of glimepiride, a poorly water-soluble antidiabetic drug, with beta-cyclodextrin and its derivatives (HP-beta-CyD and SBE-beta-CyD) in presence of different concentrations of water-soluble polymers (HPMC, PVP, PEG 4000 and PEG 6000) on the dissolution rate of the drug has been investigated. The results revealed that the dissolution rate of the drug from these ternary systems is highly dependent on polymer type and concentration. The dissolution rate of the drug from ternary systems containing PEG 4000 or PEG 6000 seems to be generally higher than from systems containing HPMC or PVP. An optimum increase in the dissolution rate of the drug was observed at a polymer concentration of 5% for PEG 4000 or PEG 6000 and at 20% concentration of HPMC or PVP. The dissolution rate of the drug from the ternary system glimepiride-HP-beta-CyD-5% PEG 4000 was high compared to the other systems. Tablets containing the drug or its equivalent amount of this ternary system were prepared and subjected to accelerated stability testing at 40 degrees C/75% R.H. to investigate the effect of storage on the chemical stability as well as therapeutic efficacy of the tablets. The results revealed stability of the tablets and consistent therapeutic efficacy on storage.

Administration, Oral↗
PubMed2006

A transdermal delivery system for glipizide.

Glipizide is one of the most commonly prescribed drugs for treatment of type 2 diabetes. Oral therapy with glipizide comprises problems of bioavailability fluctuations and may be associated with severe hypoglycaemia and gastric disturbances. As a potential for convenient, safe and effective antidiabetic therapy, the rationale of this study was to develop a transdermal delivery system for glipizide. For this purpose, inclusion complexes of the drug in beta-cyclodextrin (beta-CyD), dimethyl-beta-cyclodextrin (DM-beta-CyD), hydroxypropyl-beta-cyclodextrin (HP-beta-CyD), and hydroxypropyl-gamma-cyclodextrin (HP-gamma-CyD) were prepared. Several percutaneous formulations of the drug and the prepared complexes in different bases (o/w emulsion, polyethylene glycol, carboxymethyl cellulose and Carbopol) were developed. Release studies revealed an improved release of the drug from formulations containing glipizide-CyD complexes. Ex vivo permeation studies through full thickness rat abdominal skin were conducted, whereby the effect of several conventional penetration enhancers (propylene glycol [PG], oleic acid, urea, dimethyl sulfoxide, menthol, limonene and cineole) was monitored. Highest flux was obtained from ointments prepared with Carbopol gel base containing a combination of PG and oleic acid as well as ointments prepared in the same base utilizing glipizide-DM-beta-CyD complex and urea. In vivo studies on diabetic male Wistar rats revealed a marked therapeutic efficacy sustained for about 48 hours. In this respect, two formulations showed best biological performance. In the first formulation, the drug was incorporated in Carbopol gel base in the presence of 20% PG together with 15% oleic acid. The second was prepared by incorporating glipizide-DM-beta-CyD complex in Carbopol gel base in presence of 15% urea. The glucose tolerance test showed suppression of hyperglycaemia induced in glucose-loaded rats. The above-mentioned results might shed a strong beam of light on the feasibility of using glipizide in a transdermal delivery system for treatment of type 2 diabetes with the aim of improving both patient compliance and pathophysiology of the disease.

Acrylic Resins↗
PubMed2005

Formulation and biological evaluation of glimepiride-cyclodextrin-polymer systems.

Glimepiride is one of the third generation sulfonylureas used for treatment of type 2 diabetes. Poor aqueous solubility and slow dissolution rate of the drug lead to irreproducible clinical response or therapeutic failure in some cases due to subtherapeutic plasma drug levels. Consequently, the rationale of this study was to improve the biological performance of this drug through enhancing its solubility and dissolution rate. Inclusion complexes of glimepiride in beta-cyclodextrin (beta-CyD), hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and sulfobutylether-beta-cyclodextrin (SBE-beta-CyD), with or without water soluble polymers were prepared by the kneading method. Binary systems were characterized by thermogravimetric analysis, IR spectroscopy and X-ray diffractometry. Phase solubility diagrams revealed increase in solubility of the drug upon cyclodextrin addition, showing A(p) type plot indicating high order complexation. All the ternary systems containing beta-CyD or HP-beta-CyD showed higher dissolution efficiency compared to the corresponding binary systems. The hypoglycemic effect of the most rapidly dissolving ternary system of glimepiride-HP-beta-CyD-PEG 4000 was evaluated after oral administration in diabetic rats by measuring blood glucose levels. The results indicated that this ternary system improves significantly the therapeutic efficacy of the drug. In conclusion, the association of water soluble polymers with glimepiride-CyD systems leads to great enhancement in dissolution rate, increased duration of action and improvement of therapeutic efficacy of the drug.

Administration, Oral↗
PubMed1999

Inclusion complexation of furosemide in cyclodextrins. Part 2: Implication on bioavailability.

The effect of inclusion complexation of furosemide in cyclodextrins (CyD) on the bioavailability of the drug was studied on normal human volunteers. The excretion rate of the drug was determined by HPLC for a period of 24 h. post dosing. Several pharmacokinetic parameters were calculated and statistically analyzed. viz., peak excretion rate, peak excretion time, half peak time, elimination rate constant, area under the excretion rate time-curve as well as the total amount of drug excreted. The obtained results show that on administration of furosemide in the form of an inclusion complex in CyDs particularly beta-CyD or its dimethyl derivative may improve its biological performance, taking into consideration that furosemide is characterized by a rapid onset and a short duration of action. Inclusion complexation of furosemide in CyDs leads to a more or less delay in its onset of action, a significant increase in its duration of action as well as significant augmentation in its overall biological availability.

Adult↗
PubMed1998

Cyclodextrins in acetazolamide eye drop formulations.

The interaction of acetazolamide with beta-cyclodextrin, (beta-CD), dimethyl-beta-cyclodextrin (DM-beta-CD) and trimethyl-beta-cyclodextrin (TM-beta-CD) was monitored spectrophotometrically. The results revealed formation of equimolar complexes. The apparent solubility of acetazolamide in water was found to increase linearly with increasing CD concentration. The effect of CDs on the permeation of acetazolamide through semi-permeable membranes and the topical delivery of acetazolamide was investigated. Maximum acetazolamide penetration was obtained when just enough CD was used to keep all acetazolamide in solution. For an acetazolamide concentration of 10 mg/ml, the optimum CD concentration appeared to be 3.5 mmol/l for beta-CD, 2.8 mmol/l for TM-beta-CD and 6.0 mmol/l for DM-beta-CD. The effect of CDs on the bioavailability of acetazolamide was assessed by measuring the intraocular pressure in rabbits. The results indicated that CDs have a significant influence on the biological performance of the drug leading to augmentation in its intensity of action and bioavailability as well as prolongation in its duration of action.

Acetazolamide↗
PubMed1997

Improvement of the biological performance of oral anticoagulant drugs. 1. Warfarin.

Coevaporates of warfarin sodium containing different weight fractions of polyvinylpyrrolidone (Kollidon s5 and 30) polymers of different molecular weights were prepared and their characterization, dissolution properties as well as their bioavailability in rabbits were assessed. UV and IR spectrophotometery revealed a sort of binding between the drug and polymers. Optimum binding tendency appears at polymer weight fractions of 0.7 and 0.5 for Kollidon 25 and Kollidon 30, respectively. Incorporation of the drug with PVP enhances its dissolution properties and improves its bioavailability. Of all the investigated warfarin/PVP systems, the coevaporate of warfarin with an equal weight fraction of Kollidon 30 was found to exhibit optimum biological properties beside highest dissolution rate.

Animals↗
PubMed1997

Interaction of oral anticoagulants with methyl xanthines.

The interaction of warfarin and dicumarol with methyl xanthines was monitored. The results revealed formation of equimolar complexes with both caffeine and theophylline. The interaction is exothermic and complexation is thermodynamically unfavourable. The apparent solubility of dicumarol in water was found to increase linearly with increasing methyl xanthine concentration. The dissolution rate of the prepared complexes is higher than that of their respective physical mixtures or the respective drug per se. The implication of such interaction on the biological performance of the two anticoagulants was assessed in Albino rabbits. The results indicate that incorporation of dicumarol in form of a complex or even as a physical mixture with methyl xanthines does affect the biological performance of the drug to a marked extent.

Animals↗
PubMed1996

Improvement of some pharmaceutical properties of drugs by cyclodextrin complexation. Part 6: Ampicillin.

The potentiality of interaction of ampicillin with beta-cyclodextrin (beta-CD) was investigated by spectrophotometric and vapour pressure osmometric methods. The results revealed formation of a two-to-one inclusion complex of the drug in beta-CD. Complexation of the drug with beta-CD was found to increase both the solubility as well as the dissolution rate of the drug. On the other hand, assessment of bioavailability in human subjects depicted highly significant increase in both the rate and extent of absorption of the drug.

Adjuvants, Pharmaceutic↗
PubMed1996

Discrepancy among dissolution rates of commercial tablets as a function of dissolution method. part 6: rifampicin.

The dissolution rate of six batches of commercial rifampicin products manufactured by three pharmaceutical companies was determined by both closed and open dissolution systems. The most consistent results were those obtained by the beaker method. Inter-batch as well as inter-brand variation in dissolution were found to be more evidently detected and evaluated by adopting the beaker and flow-through methods. The biovailability of these products was assessed in human subjects according to a cross-over design system. Based on the values of the correlation coefficient of the in vitro results obtained by different dissolution methods with the in vivo results, the USP rotating basket method appears to correlate best with maximum urinary excretion rate, area under excretion rate versus time curve as well as total amount of drug excreted. Thus, determination of the dissolution rate of rifampicin products by the USP rotating basket method can be considered as a reliable tool for predicting the in vivo performance of the drug.

Antibiotics, Antitubercular↗
PubMed1996

Improvement of some pharmaceutical properties of drugs by cyclodextrin complexation. 5. Theophylline.

The interaction of theophylline (TPH) with beta-cyclodextrin (beta-CD) was investigated by spectrophotometry, vapour pressure osmometry and DSC. The results revealed a molecular interaction between TPH and beta-CD. The continuous variation method was used to elucidate the stoichiometry of such an interaction by spectrophotometric as well as vapour pressure measurements. Both types of data revealed the formation of two-to-one TPH/beta-CD complex. The stability constant of the complex was determined at different temperatures by the vapour pressure osmometric method. The enthalpy and entropy of the interaction were evaluated and the results indicate the liberation of little heat during complexation and the disorder of the guest molecule upon complexation. The effect of beta-CD on the solubility of TPH indicates that beta-CD exhibits a definite solubilizing effect towards the drug with a typical Bs isotherm. The stability constant of the complex and the amount of drug solubilized in the form of complex reveal that complex-formation is the only factor governing the solubilizing effect of beta-CD towards the drug. The dissolution rates of TPH, TPH/beta-CD physical mixture as well as the prepared complex were determined according to U.S.P. method and at pH 1.2. In both cases, the dissolution profile of the complex reveals enhanced dissolution properties compared to the drug. The effect of beta-CD on the partition properties of TPH reveals decrease in presence of beta-CD. The effect of beta-CD on the bioavailability of TPH was investigated in human subjects. A clear difference in the biological performance between the drug and the complex was revealed. The pharmacokinetic parameters including Cmax, tmax, Cmin, t1/2, Ke, MRT and AUC revealed that inclusion complexation of theophylline in B-cyclodextrin results in not only an improvement in the bioavailability of the drug, but also to acquired sustained release properties for the drug.

Adult↗
PubMed1995

Improvement of some pharmaceutical properties of drugs by cyclodextrin complexation. 3. Bromhexine hydrochloride.

The potentiality of interaction of bromhexine (1) with beta-cyclodextrin was investigated by spectrophotometric methods. Differential UV spectrophotometry revealed a decrease in the optical density of the drug in presence of beta-cyclodextrin (beta-CD) and a hypsochromic shift in one of the two wavelengths of maximum absorption of the drug from 312 to 309 nm in presence of beta-CD. The continuous variation method based on spectrophotometric measurements revealed the formation of 1:1 complex between the drug and beta-CD. The solubility of 1 in presence of beta-CD was found to increase to a marked extent. Also the dissolution profiles of the drug, physical mixture of the drug and beta-CD as well as the prepared complex showed a great enhancement of the dissolution properties of 1 in presence of beta-CD either in a physical mixture or in complexed state. The partition coefficient between n-octanol and phosphate buffer of pH 7.4 of 1 and its beta-CD complex was also determined. Investigation of the transdermal diffusion of the drug and the complex in different dermatological vehicles was carried out using abdominal rat skin. A linear relationship was found to exist between the amount of drug released and the square root of the time. The drug showed the highest release characteristics from methyl cellulose > PVP > PEG 400, also inclusion complexation of 1 in beta-CD causes an improvement in the release properties of the drug from the investigated dermatological vehicles.

Administration, Cutaneous↗
PubMed1995

Improvement of some pharmaceutical properties of drugs by cyclodextrin complexation. 1. Allopurinol.

The potentiality of molecular interaction of allopurinol (1) with beta-cyclodextrin (beta-CD) was investigated by spectrophotometric methods. Differential UV spectrophotometry revealed an increase in the optical density of 1 in presence of beta-CD. Application of the continuous variation method to spectrophotometric measurements was attempted and revealed the formation of an 1:1 complex between 1 and beta-CD. The apparent solubility of the drug in presence of beta-CD was investigated at different temperatures. The solubility-potentiating effect increases with increasing beta-CD concentration at 25-45 degrees C. On the other hand, the solubility of 1 decreases in presence of beta-CD at 60 degrees C. The amount of drug solubilized in the form of the complex was determined at different temperatures and the results revealed that the solubilizing effect of beta-CD is entirely due to complex-formation. The stability constant of the complex was determined at different temperatures. The enthalpy and entropy of interaction were also computed from the values of the stability constant of the complex at different temperatures. The large negative enthalpic value indicates a strong involvement of dipoles and van der Waals interaction during complexation. The dissolution profiles of the drug, physical mixture of the drug and beta-CD as well as the prepared complex show an enhancement of drug dissolution from the prepared complex or the physical mixture compared to the drug per se which reveals an improvement of the dissolution property of 1 by beta-CD complexation.

Allopurinol↗
PubMed1995

Improvement of some pharmaceutical properties of drugs by cyclodextrin complexation. 4. Chlorpromazine hydrochloride.

The potentiality of interaction of chlorpromazine hydrochloride (CPZ) with beta-cyclodextrin (beta-CD) was investigated by spectrophotometry, vapour pressure osmometry and DSC thermograms. The results revealed a very strong evidence for molecular interaction between CPZ and beta-CD. The continuous variation method was used to elucidate the stoichiometry of such interaction by spectrophotometric as well as vapour pressure measurements. Both types of data revealed the formation of a 1:1 complex. The stability constant of the complex was determined at different temperatures by the vapour pressure osmometric method. The enthalpy and entropy of interaction were evaluated and the results indicate that the interaction is exothermic. The CPZ/beta-CD complex was prepared, lyophilized and photochemical stability of the drug, its physical mixture with beta-CD as well as the prepared complex was investigated at different pH-values in presence of different buffer systems. The results revealed that the stability of the drug is greatly improved in presence of beta-CD and the great dependency of stability on the pH of the solution is decreased in presence of beta-CD. The partition coefficient of CPZ and its complex with beta-CD was determined. The data reveal a higher p.c. of the complex compared to the parent drug. The effect of beta-CD on the bioavailability of CPZ was investigated by measuring the miotic response intensity in volunteers receiving a single oral dose of the drug, drug/beta-CD physical mixture or complex. The results revealed a distinct improvement of the biological performance of CPZ by beta-CD as evidenced by an increased intensity of drug action and its duration as well as augmenting its bioavailability without affecting the time for maximum effect.

Adult↗
PubMed1993

Discrepancy among dissolution rates of commercial tablets as a function of dissolution method. Part 5: In vitro/in vivo correlation for chlorpromazine hydrochloride tablets.

The bioavailability of seven commercially available batches of chlorpromazine hydrochloride tablets belonging to three different brands was assessed by measuring the intensity of miotic response to the tablets in six normal human subjects according to a cross-over design system. The following pharmacodynamic parameters were computed, viz., maximum miotic response intensity, tmax, half-peak time as well as the area under the percentage miotic response intensity versus time curve from time 0 to 8 h. Attempts to correlate two in vitro dissolution parameters, that is, dissolution efficiency and percentage weight of drug dissolved after 30 min to the in vivo parameter of the area under percentage miotic response intensity versus time curve revealed that the second in vitro parameter correlates better than the first one with the in vivo parameter regardless of the dissolution method. On the other hand, the two in vitro dissolution parameters obtained by the USP rotating basket method show good correlation with the in vivo parameter.

Adult↗
PubMed1982

Effect of chelating agents on the stability of injectable isoniazid solutions.

The chelating agents NTA, EDTA, HEDTA and DTPA afford a stabilizing action towards isoniazid solutions. The stabilizing effect of the chelating agents is highly dependent on their concentration. The stability of isoniazid solutions increases markedly with increasing NTA or EDTA concentration up to 1 mmol/l. Beyond this concentration, the stabilizing effect of NTA is more or less independent of its concentration and the dependency of the degradation rate of isoniazid on the concentration of EDTA becomes less pronounced. There is an optimum concentration for HEDTA and DTPA at which their stabilizing effect is maximum; below or above this concentration, the stability of isoniazid decreases. The stabilizing efficiency of the investigated chelating agents decreases in the order DTPA greater than HEDTA greater than EDTA greater than NTA, which runs parallel with the stability constants of their metal chelates.

Chelating Agents↗
PubMed1977

A paper chromatographic method for separation and determination of synephrine in injectable solutions.

A new analytical method using ascending paper chromatographic technique was developed for identification and quantitative determination of residual synephrine in fresh and deteriorated samples. This method was found to be stability indicating; one to five degradation products have been successfully separated from drug samples subjected to accelerated stability testing at 60 degrees C for 3 months.

Chromatography, Paper↗