Enhancement of dissolution rate, pharmacokinetic evaluation, and study the effect of renal impairment on the absorption of ethoxazine hydrochloride

In this study, coprecipitation and fusion techniques were applied to prepare ethoxazene hydrochloride solid dispersion using different polymers viz PVP'S [PVP K90, PVP K25 and PVP K17] and PEG'S [PEG 6000, PEG 4000 and PEG 1500] in the concentration of 1:1, 1:2 and 1:3 drug polymer ratio. A dissolution testing of the drug with the previously mentioned polymers was carried out in 0.1 N HCl. A kinetic treatment of the dissolution data of ethoxazene hydrochloride was carried out. The mechanism of the possible drug-polymer interaction was studied using ultraviolet, infrared spectroscopy and thin layer chromatography. Dispersion of the drug into a matrix either by fusion or coprecipitation techniques led to an increase in the dissolution rate and extent of the drug. The kinetic treatment of the dissolution rate of ethoxazene hydrochloride showed that the dissolution followed first order kinetics. Ultraviolet spectroscopy, infrared spectroscopy, thin layer chromatography and differential scanning calorimetry revealed that there was no complex or any interaction between the drug and any of the used polymers. The enhancement of the dissolution rate of the drug was due to an increased solubility of the drug in the dissolution layer, reduction in the particle size and high-energy solid formation of the drug

Chitinase-bile salts complexes: a new approach for management of Hypercholesterolemia

The interaction of chitosan and both sodium cholate and sodium deoxycholate was evaluated by viscosity measurement, differential scanning calorimetry [DSC] and Fourier-transform infrared [FT-IR] spectroscopy. The binding ratio of chitosan with sodium cholate or sodium deoxycholate was found to be 1: 10. DSC and IR studies revealed that chitosan forms complexes with both sodium cholate and deoxycholate. The effect of chitosan on serum cholesterol, triglycerides, and lipoproteins levels was also studied in rats fed with 2% cholesterol supplemented diet. Oral administration of chitosan in a dose of 1 g/kg body weight mixed with the cholesterol supplemented diet daily for 14 days resulted in significant decrease in total cholesterol and low-density lipoprotein-cholesterol levels [P <0.01] compared with the group received cholesterol supplemented diet alone. Serum triglycerides and high-density lipoprotein-cholesterol levels were not significantly affected. Since chitosan has extremely low toxicity and commonly used in sustained release dosage forms, these results encourage clinical trials of chitosan in treatment of hypercholesterolemia, atherosclerosis and related disorders

Modified methods for direct assay of levonorgestrel and prolactin levels during two monthly injections

Modified radioimmunoassay [RIA] and chemiluminescence [CL] methods were adapted for ultra-micro determination of levonorgestrel [L- Nog] and prolactin [PRL] in biological fluids. No prior extraction was needed. The methods yielded precise results with coefficient of variation of < 10%. The methods correlated well with USP XXIII and the conventional RIA methods. The correlation coefficients [r] were 0.92, 0.94 for L-Nog and 0.91 for PRL. The sensitivity of modified RIA for L-Nog was 100 Pmol/L. Modified CL method for PRL showed excellent sensitivity [0.04 ng/ml]. Modified methods were applied to quantitate L-Nog and PRL serum levels during two monthly L-Nog injection. The modified analytical techniques provided accurate, precise, time saving and sensitive methods for analysis of L-Nog and PRL serum levels

Determination of some levels of glucose and some minerals during treatment with injectable contraceptives

Serum sodium [Na], potassium [K], total calcium, iron and glucose levels, during two monthly injections of levonorgestrel [L-Nog] and norethisterone enanthate [NET-EN] were determined. Ion selective electrode potentiometric method for analysis of Na and K yielded more precise results than flame photometry. The intra- and intercoefficients of variation [CV] ranged from 0.5 to 1.1%, 0.6 to 1.9%, 0.6 to 1.9% and 2.0 to 2.3% for Na and K, respectively. Modifications of ferrozine method for analysis of serum iron were introduced. The modified method correlated well with reference bathophen-anthroline method, correlation coefficient [r] was 0.95. Precision was acceptable, intra- and inter CV ranged from 2.1 to 3.4% and 2.6 to 3.9%, respectively. Linearity was kept up to 2500 mug/dl, recovery was 98.8% +/- 1.4 and sensitivity was 20 mug/dl. The only significant change in the studied serum minerals and glucose levels was an increase in iron level, which was beneficial. The modified ferrozine method proved to be an accurate and reliable method for serum iron analysis

Pharmacokinetic studies of SHAM capsules

Urinary excretion data of salicylhydroxamic acid [SHAM] on human volunteers were used to compute its pharmacokinetic parameters. HPLC method was used to determine drug content in urine. The study revealed that, the drug is rapidly absorbed and excreted. The absorption half life of the drug ranged between 15.2-23.2 min. While, its urinary elimination t1/2 was in the range of 23.1 to 42.2 min. The amount of the drug eliminated in urine reaches to about 75% of the oral dose administrated proving SHAM efficiency as antilithiatic drug. On the other hand, the drug is hardly detected in urine after 6 hours indicating a thorough revision of dosage regimen

Some reactions of 4-chloro and 4-hydrazino 2- [naphthylmethyl] quinazoline

The considerable biological and medicinal activities of quinazoline derivatives as anti-inflammatory[1], antihypertensive[2] hypnotic[3] anti-adrenergic[4] and as fungicides[5] have stimulated the recent interest in the synthesis of derivatives of these ring systems. In continuation of our previous work [6] we have investigated a variety of synthetic routes to a number of quinazoline derivatives. Thus, we have found that the reaction of 4-chloro-2- [a-naphthylmethyl]-quinazoline [1] with aniline, benzylamine, and hydrazine hydrate in boiling butanol gives the corresponding 4-[anilino, benzylamino and hydrazino]-2- [alpha -naphthyl methyl]-quinazolines [2a-c]. However, treatment of [1] with sodium azide in boiling acetic acid gave the corresponding tetrazoloquinazoline derivatives[3]. Refluxing of [1] with acylhdrazines, namely cyanoacetyl hydrazine and benzoylhydrazine in boiling butanol gave the corresponding 3-[cyanomethyl or phenyl]-triazolo [3,4-a]-5 [alpha -naphthyl methyl]-quinazoline [4a and b]. In a recent series of publications [7,8], it has been reported that, the reaction of 4-chloroquinazoline with amino acids gave imidazo quinazoline derivatives. In the present investigation, the reaction of [1] with glycine in boiling butanol and the ring closure by Ac[2]O yielding 5-oxo-imidazo [3,4-a] -2- [[alpha -naphthyl methyl]-quinazoline [5]. Recently [6,9], It has been proved that 4-chloro-quinazoline is a useful precursor in the synthesis of fused nitrogen bridged benzopyrimidinoquinazoline. Similarly, we found that treatment of [1] with anthranilic acid in boiling butanol gave benzopyrimidinoquinazoline [6]

Comparison of the microbiological turbidimetric and hydroxylamine colorimetric methods in stability study of cefadroxil monohydrate powder

Comparison between the chemical and microbiological methods for the analysis of cefadroxil in powder for reconstitution stored at different temperature was carried out. Results indicated that the values of the antibiotic percent obtained by chemical method differ than those obtained microbiologically of the same samples. Microbiological assay of stored samples at 25 gave information that the product is valid up to 30 months while the chemical method indicated that the same sample valid for 12 months only. Sample stored at 37C seemed valid after storage for 12 months using microbiological method but the chemical assay indicated that it was not valid after 6 months. Chemical and microbiological assay indicated that stored samples at 56C were not valid but there was difference between values obtained by chemical and microbiological methods. Microbiological assay of stored sample valid for 2 months but chemical assay showed them not valid at all. This indicated that the chemical method considered invalid for stability study and/or assessment of validity of product containing cefadroxil