G.S EF, S.K A-E, F.I. AA. Microemulsion Versus Niosomes For The Transdermal Delivery Of Repaglinide. Asian Journal of Pharmaceutical & Health Sciences. 2012;2(4):526.Abstract

<p>The antidiabetic drug, Repaglinide, was incorporated into a microemulsion and a niosomal carriers for transdermal administration to overcome the drawbacks associated with its oral formula. In the microemulsion formulation, pseudoternary phase diagrams were constructed to obtain the concentration range of the oil, surfactant (S) and co-surfactant (CoS) using three different S/CoS weight ratios. Microemulsion showed spherical particles with mean diameter ranging from 40.60 ± 13.04 to 58.94±0.02 nm and newtonian viscosity ranging from 58.94 ± 0.02 to 111.23±6.32 mPa.S. Compared to the marketed tablet, the release of repaglinide from microemulsion showed a zero order, controlled and continuous pattern. Repaglinide was also encapsulated in niosomal formulations. Niosomes showed vesicle size diameter ranging from 109 ± 6.2 to 263±11.9 nm with an entrapment efficiency of 77.9 ± 5.2 to 98.6±6.3 %. Compared to the oral tablet, release of repaglinide from niosomal vesicles showed a more uniform pattern however, a much slower rate. The microemulsion formulation (ME1) composed of triacetin as oil, Cremophor® RH40 and n-butanol as surfactant and co-surfactant, respectively, together with niosomal formulation (S) prepared using span 60 and cholesterol in ratio 1:1 were selected for the ex-vivo permeation. The permeation rate constant and permeation efficiency were found to be 65.5 μg/cm²/h and 29.19%, respectively with micro emulsion ME1 and 11.42 μg/cm²/h and 4.14 %, respectively with niosomal preparation S. It was concluded that the microemulsion transdermal delivery systems offered a controlled and more sustained drug release and permeation profiles compared to the niosomal formulations and to the commercial tablet.</p>

A.-H.I ME, M.S M, S A-S, G.S. E-F. Pharmacogenetics-Oriented Therapeutic Drug Monitoring of Digoxin in Critically Ill Patients. Saudi Pharmaceutical Journal . 2006;14:139-148.Abstract

<p><span style="font-size: small;">This study was performed to outline the different MDR-1 (Multi-Drug Resistance-1) genotypes in a sample of 37 Egyptian patients, suffering from atrial fibrillation (AF) and/or congestive heart failure (CHF) and are using digoxin, to assess the role of MDR-1 genotypes polymorphism in affecting steady state serum digoxin therapeutic levels, and studying the consequences on patients' clinical outcome. Two venous blood samples were drawn from each patient; the 1st sample was taken, on admission, for DNA extraction and genotyping and the 2nd was taken, 6 hours post dose after reaching steady state concentration, for serum digoxin assay. Serum digoxin levels were assayed using EMIT 2000 analyzer, and MDR-1 genotyping was done using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Twenty patients (54.1%) showed serum digoxin levels within the therapeutic range, 12 patients (32.4%) showed serum digoxin levels under the minimum effective concentration (&lt; 0.9 ng/ml), while 5 patients (13.5%) showed serum digoxin levels over maximum safety concentration (&gt; 2 ng/ml), with P value of 0.0001 among the three groups. MDR-1 genotyping revealed ten patients (27%) carrying the homozygous mutant TT genotype, 27 patients (73%) carrying the heterozygous mutant CT genotype, with no patient showing the wild CC genotype. Allelic distribution showed 42% for the wild type C allele while 58% for the homozygous mutant T allele. Patients carrying the homozygous mutant TT genotype showed significantly lower serum digoxin levels compared with those carrying the heterozygous mutant CT genotype (P value: 0.009). Patients with significant improvement carried the CT genotype and had serum digoxin levels within the therapeutic range. In conclusion, patients with different MDR-1 genotypes had variations in their serum digoxin levels and identification of MDR-1 variations was found useful in predicting therapy outcome. We recommend further extensive work on large samples to study the important role of MDR-1 gene in affecting the disposition of different substrates, to be able for individualizing them according to the patients' genetic profile in order to improve drug therapy and reduce inter-patient variability</span></p>