Quality Attributes and In Vitro Bioequivalence of Different Brands of Amoxicillin Trihydrate Tablets

The purpose of this work is to explore the predictive ability of the biopharmaceutics classification system (BCS) biowaiver based on the dissolution methods for two pravastatin test products, where one of them showed bioequivalence (BE) while the other test failed (non-bioequivalence, or NBE), and to explore the reasons for the BE failure. Experimental solubility and permeability data confirmed that pravastatin is a BCS class III compound. The permeability experiments confirmed that the NBE formulation significantly increased pravastatin permeability, and could explain its higher absorption rate and higher Cmax. This finding highlights the relevance of requiring similar excipients for BCS class III drugs. The BCS-based biowaiver dissolution tests at pH 1.2, 4.5, and 6.8, with the paddle apparatus at 50 rpm in 900 mL media, were not able to detect differences in pravastatin products, although the NBE formulation exhibited a more rapid dissolution at earlier sampling times. Dissolution tests conducted in 500 mL did not achieve complete dissolution, and both formulations were dissimilar because the amount dissolved at 15 min was less than 85%. The difference was less than 10% at pH 1.2 and 4.5, while at pH 6.8 f2, results reflected the Cmax rank order.

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“…The dissolution profiles were compared by f 2 (similarity factor) [18,19]. The f 2 calculations were performed in Microsoft Excel (2016) [20].…”

Section: Dissolution Assaysmentioning

confidence: 99%

Investigation to Explain Bioequivalence Failure in Pravastatin Immediate-Release Products

et al. 2019

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“…Therefore, this system has been widely used since its inception in 1995 by Amidon et al, with adoption by various regulatory agencies [3]. Normally, for establishing bioequivalence, the calculated 90% confidence interval of the ratios for area under the drug concentration-time curve (AUC) and maximum concentration (C max ) of the test and reference products should fall within 80% to 125% of the point estimate [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…To provide evidence, the difference factor (ƒ1) and similarity factor (ƒ2) can be used. If the drug dissolution from the tested products is at least 85% within 15 min in different dissolution media, then these factors need not be calculated, as the products' bioequivalence is self-evident, because the drug formulation will be in solution form once it reaches the duodenum [4]. There has been a debate as to whether the point estimate ƒ2 is reliable when there is a significant batch-to-batch variation, and bootstrap confidence intervals for ƒ2 have therefore been suggested [8].…”

Section: Introductionmentioning

confidence: 99%

In Vitro Dissolution and in Silico Modeling Shortcuts in Bioequivalence Testing

Al-Tabakha

Alomar

2020

Pharmaceutics

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Purpose: To review in vitro testing and simulation platforms that are in current use to predict in vivo performances of generic products as well as other situations to provide evidence for biowaiver and support drug formulations development. Methods: Pubmed and Google Scholar databases were used to review published literature over the past 10 years. The terms used were “simulation AND bioequivalence” and “modeling AND bioequivalence” in the title field of databases, followed by screening, and then reviewing. Results: A total of 22 research papers were reviewed. Computer simulation using software such as GastroPlus™, PK-Sim® and SimCyp® find applications in drug modeling. Considering the wide use of optimization for in silico predictions to fit observed data, a careful review of publications is required to validate the reliability of these platforms. For immediate release (IR) drug products belonging to the Biopharmaceutics Classification System (BCS) classes I and III, difference factor (ƒ1) and similarity factor (ƒ2) are calculated from the in vitro dissolution data of drug formulations to support biowaiver; however, this method can be more discriminatory and may not be useful for all dissolution profiles. Conclusions: Computer simulation platforms need to improve their mechanistic physiologically based pharmacokinetic (PBPK) modeling, and if prospectively validated within a small percentage of error from the observed clinical data, they can be valuable tools in bioequivalence (BE) testing and formulation development.

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“…The upsurge of pharmaceutical industries with lower scrutiny or inspection of manufacturers whose existence has been encouraged by the affordability of generic brands, creating room for the manufacture and circulation of substandard products as well as administration of generic antibiotics at sub-therapeutic/sub-inhibitory doses has been implicated in antibiotic resistance 4,5 . Some researchers 6,7,8,9 opine that generic drugs may not be therapeutically equivalent to the innovator products and therefore may not be as effective.…”

Section: Introductionmentioning

confidence: 99%

“…The similarity factor (f2) although more complicated to calculate and more time consuming to obtain data for, assesses the in vitro bioequivalence of innovator and generic or test drug products and estimates expected drug levels in humans (in-vitro -in-vivo correlation) using in-vitro dissolution profiles which is not obtainable with general physicochemical testing. The FDA considers in-vitro dissolution testing to be more discriminating than an in-vivo test 4,26 .…”

Section: Introductionmentioning

confidence: 99%

Untitled

2018

IJPSR

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Counterfeit and substandard pharmaceutical products circulate widely in developing countries, yet adequate techniques to monitor quality is lacking. We report herein a quick and reliable approach to predict the in-vitro bioequivalence and interchangeability of common antibiotics using nine model drugs; four brands of azithromycin and five brands of clarithromycin tablets marketed in Nigeria. Pharmacopoeia guidelines (British and United States) were used to assess tablet quality such as friability, disintegration and dissolution times. All the brands tested passed the British Pharmacopoeia standard for disintegration time and their hardness and friability values were also considered adequate. There were no significant differences in the dissolution profiles of the brands, however, the azithromycin brands released >70% of the active drug within 30 min. The calculated similarity factor values for the azithromycin and clarithromycin brands were between 61 to 100 and 46 to 100 respectively. Based on the in-vitro tests, all the brands of azithromycin were considered bioequivalent with the innovator brand. However, only one brand had a similarity factor very close to that of the innovator brand and could be considered interchangeable. All the brands of clarithromycin were also considered bioequivalent, except one brand. Our results show that, the concept of dissolution efficiency could be a reliable method of predicting bioequivalence of antibiotics thereby serving as a tool to monitor and prevent the circulation of fake and counterfeited drug products.

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Quality Attributes and In Vitro Bioequivalence of Different Brands of Amoxicillin Trihydrate Tablets

Cited by 18 publications

References 27 publications

Investigation to Explain Bioequivalence Failure in Pravastatin Immediate-Release Products

Investigation to Explain Bioequivalence Failure in Pravastatin Immediate-Release Products

In Vitro Dissolution and in Silico Modeling Shortcuts in Bioequivalence Testing

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