In vitro dissolution profile comparison--statistics and analysis of the similarity factor, f2.
ABSTRACT To describe the properties of the similarity factor (f2) as a measure for assessing the similarity of two dissolution profiles. Discuss the statistical properties of the estimate based on sample means.
The f2 metrics and the decision rule is evaluated using examples of dissolution profiles. The confidence interval is calculated using bootstrapping method. The bias of the estimate using sample mean dissolution is evaluated.
1. f2 values were found to be sensitive to number of sample points, after the dissolution plateau has been reached. 2. The statistical evaluation of f2 could be made using 90% confidence interval approach. 3. The statistical distribution of f2 metrics could be simulated using 'Bootstrap' method. A relatively robust distribution could be obtained after more than 500 'Bootstraps'. 4. A statistical 'bias correction' was found to reduce the bias.
The similarity factor f2 is a simple measure for the comparison of two dissolution profiles. But the commonly used similarity factor estimate f2 is a biased and conservative estimate of f2. The bootstrap approach is a useful tool to simulate the confidence interval.
- SourceAvailable from: Ahmed El-AshmawyInternational Journal of Pharmacy and Pharmaceutical Sciences 01/2014; · 1.59 Impact Factor
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ABSTRACT: Objective: This research purposed to describe and evaluate the influence of magnesium stearate (MgSt), purified talc (talc) and combination of both (MgSt-PT) on ternary/quaternary mixture of freely and poorly water-soluble drug. Methods: Chlorpheniramine maleate (CPM) and prednisone (PDN) were used as the drug model of freely and poorly water-soluble drug, respectively. Compatibility studies between drugs and lubricants were carried out using Fourier transform infrared spectroscopy (FTIR). Ternary/quaternary interactive mixture of drugs, lubricants and carriers were conducted using granules of lactose-starch (1:1) as carriers with particle size 250 – 425 µm. Characterizations were conducted by homogeneity of mixture, physical properties of granules and tablets and drug releases. The results were analyzed statistically using one-way analysis of variance (ANOVA) with 95% of confidence interval level and dependent method for drug release. Results: Homogeneity of binary mixture within drug and carrier was achieved in 60 minutes with 20 revolutions per minute. MgSt, talc and combination of both provided stable ternary/quaternary interactive mixture. MgSt affected the reduction of compactibility, prolong the disintegration time, retardation the drug release and talc improved flowability. Conclusion: Talc provided more preferable effects than MgSt, and combination of both lubricants showed desirable physical properties of tablet. MgSt, talc and combination of both provided no significant effect on physical properties and drug release of CPM as freely water-soluble drug and the significant effect was observed on PDN as poorly water-soluble drug.International Journal of Pharmacy and Pharmaceutical Sciences 01/2015; 7(1):398. · 1.59 Impact Factor
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ABSTRACT: Rifaximin is an antibiotic, acting locally in the gastrointestinal tract, which may exist in different crystal as well as amorphous forms. The current marketed rifaximin formulation contains polymorph alpha, the systemic bioavailability of which is very limited. This study compared the pharmacokinetics of this formulation with those of the amorphous form. Amorphous rifaximin was specifically prepared for the study and formulated as the marketed product. Two doses (200 mg and 400 mg) of both formulations were given to two groups of 12 healthy volunteers of either sex according to a single-blind, randomized, two-treatment, single-dose, two-period, cross-over design. Plasma and urine samples were collected at preset times (for 24 hours or 48 hours, respectively) after dosing, and assayed for rifaximin concentrations by high-performance liquid chromatography-mass spectrometry. For both dose levels, peak plasma concentration, area under the concentration-time curve, and cumulative urinary excretion were significantly higher after administration of amorphous rifaximin than rifaximin-α. Ninety percent confidence intervals for peak plasma concentration, area under the concentration-time curve, and urinary excretion ratios were largely outside the upper limit of the accepted (0.80-1.25) range, indicating higher systemic bioavailability of the amorphous rifaximin. The few adverse events recorded were not serious and not related to the study medications. Rifaximin-α, a crystal polymorph, does differ from the amorphous form, the latter being systemically more bioavailable. In this regard, care must be taken when using - as a medicinal product - a formulation containing even small amounts of amorphous form, which may alter the peculiar pharmacologic properties of this poorly absorbed antibiotic.Drug Design, Development and Therapy 01/2015; 9:1-11. · 3.03 Impact Factor