In Vitro Dissolution of Generic Immediate-Release Solid Oral Dosage Forms Containing BCS Class I Drugs: Comparative Assessment of Metronidazole, Zidovudine, and Amoxicillin Versus Relevant Comparator Pharmaceutical Products in South Africa and India

Reddy, Nallagundla H. S.; Patnala, Srinivas; Löbenberg, Raimar; Kanfer, Isadore

doi:10.1208/s12249-014-0135-6

Cited by 34 publications

(30 citation statements)

References 5 publications

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“…If both products are very rapidly dissolving, further dissolution profile comparison using f 2 calculation is not necessary for similarity assessment (4). This result is consistent with a previous study done by Reddy et al, in which the same test product and the same comparator product showed very rapid dissolution (10). However, according to Löbenberg et al, metronidazole tablets manufactured by Sanofi-Aventis (Flagyl) required 60 min to release more than 85% of its dose (11).…”

Section: In Vitro Dissolution Testingsupporting

confidence: 91%

“…However, according to Löbenberg et al, metronidazole tablets manufactured by Sanofi-Aventis (Flagyl) required 60 min to release more than 85% of its dose (11). Even though there are similarities among the products studied by us and by Reddy et al and Löbenberg et al, the differences in the percentage of drug release findings by Löbenberg et al, may be due to several variables, such as the characteristics of the active pharmaceutical ingredient or the quality and composition of the excipient (10,11). The disintegration time was 5 minutes for both these products.…”

Section: In Vitro Dissolution Testingmentioning

confidence: 90%

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Application of Biowaiver Methodology for a Post-Marketing Study of Generic and Brand Name Metronidazole Tablets

Thambavita¹,

Fernando²,

Galappatthy³

et al. 2018

Dissolution Technol

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An important component of evaluation of generic medicines is assessing their therapeutic equivalence, which is done by a comparative study with an appropriate comparator, such as an in vivo bioequivalence study or an in vitro dissolution study. In vivo bioequivalence studies are cumbersome and expensive. Their need might be waived using in vitro dissolution for selected drugs. In this post marketing study, we conducted in vitro dissolution testing according to the WHO guideline for biowaiver studies comparing a generic metronidazole product available in Sri Lanka with an appropriate comparator. The results showed that both products complied with the pharmacopoeial specifications, and that the generic (test) product is similar to the comparator product, with very rapid dissolution properties. In vitro dissolution of the test product was similar to the comparator in media with pH 1.2, 4.5, and 6.8, representing gastric, duodenal, and jejunal conditions. Based on the study findings, the tested metronidazole product demonstrates in vitro equivalence to the comparator product. Similarity of the dissolution profile indicates high probability of in vivo bioequivalence of the generic product compared to the brand name product, in the absence of bioequivalence data. According to the International Pharmaceutical Federation (FIP) biowaiver monograph for metronidazole, the quality and quantity of the excipient also needs evaluation for the two products to be considered therapeutically equivalent. Therefore, if the excipient composition is available, the decision of interchangeability of the two products could be made.

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Section: In Vitro Dissolution Testingsupporting

confidence: 91%

Section: In Vitro Dissolution Testingmentioning

confidence: 90%

Application of Biowaiver Methodology for a Post-Marketing Study of Generic and Brand Name Metronidazole Tablets

Thambavita¹,

Fernando²,

Galappatthy³

et al. 2018

Dissolution Technol

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“…Previously a study was conducted to compare various brands of metronidazole to comparator pharmaceutical product (Innovator or reference brand) and found none of tested metronidazole product in-vitro equivalent 16 . Another study resulted only 8 out of 11 metronidazole tested products resulted as very rapidly dissolving as defined by the WHO, whereas 2 of them failed f 2 acceptance criteria in pH 6.8 7 . In-vitro dissolution was used in several studies for therapeutic equivalence of metronidazole tablets, a study from Nigeria showed 8 out of 12 tested brands of metronidazole in-vitro equivalent 17 , a study published revealed all tested brands found equivalent and can be use as substitution 18 .…”

Section: Discussionmentioning

confidence: 98%

“…Therapeutically equivalent drug products are considered if they meet the regulatory criteria of pharmaceutical equivalence and bioequivalence [3][4][5][6][7] . For determination of therapeutic effectiveness, the aspects of safety, quality and purity has to be evaluated.…”

Section: Quick Response Codementioning

confidence: 99%

Untitled

2017

IJPSR

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ABSTRACT:Metronidazole is a class I drug in biopharmaceutics classification system (BCS) and widely used in Pakistan, various available brands in local markets along with innovator brand to serve a large population. In-vitro dissolution testing can be used as waiver for in-vivo bioequivalence studies of generic brand interchangeability for Class I drugs i.e., highly soluble and highly permeable. The objective of the study was to determine immediate release tablet dosage form of metronidazole to fulfil the requirements of 85% drug release in pH 1.2, 4.5 and 6.8 recommended by WHO. In this study physicochemical quality attributes, price comparison and dissolution studies were performed on three available brands of metronidazole 400 mg, one of them is innovator brand and the two others are test brands. The dissolution profiles were compared by using similarity factor (f 2 ) that were analyzed by UV spectrophotometer at 278 nm wavelength. The test brands were very cheap in cost as compared to innovator brand but both the test brand were failed the dissolution test in all mediums and only innovator brand showed 85% drug release within 30 minutes. The study suggested test brands are not equivalent or similar to innovator brand. In-vivo bioequivalence studies are thus needed for test brands to strengthen this invitro finding.

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“…Drug products are considered therapeutically equivalent if they meet the regulatory criteria of pharmaceutical equivalence and bioequivalence (2)(3)(4)(5)(6). Generic pharmaceutical equivalents should contain the same active ingredient(s) manufactured in the same dosage form and administered in the same pathway.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Dissolution Similarity as a Surrogate for In Vivo Bioavailability and Therapeutic Equivalence

Helmy¹,

Bedaiwy²

2016

Dissolution Technol.

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Generic immediate-release solid oral dosage forms containing BCS Class I and III drugs that have similar in vitro dissolution profiles might receive market authorization without in vivo bioequivalence testing. The objective was to investigate whether the different immediate-release generic products containing BCS Class I drugs (fluoxetine and linezolid) and a Class III drug (fluconazole) fulfill the requirements of 85% or more drug release in 15 or 30 min in all three buffers (pH 1.2, pH 4.5, and pH 6.8) using in vitro dissolution testing in accordance with WHO requirements. The dissolution profiles were compared statistically to the relevant reference product by calculating the fit factors (f 1 and f 2 ), dissolution efficiencies, and mean dissolution time. The amount of drug dissolved in all dissolution media was determined by a validated UV spectrophotometric method. All investigated products of fluoxetine and linezolid met the biowaiver criteria for BCS Class I drugs and would be considered in vitro equivalent. Only one product of the BCS Class III drug fluconazole did not pass the WHO guideline for in vitro equivalence; however, all the products released fluconazole satisfactorily, with at least 80% dissolved within 30 min. Pharmaceutical equivalence together with in vitro dissolution similarity could be considered suitable to ensure in vivo bioequivalence and, hence, therapeutic equivalence of BCS Class I and III drugs. Not all generic products containing the same drug (BCS Class I or III) in similar strengths and dosage forms are in vitro equivalent.

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In Vitro Dissolution of Generic Immediate-Release Solid Oral Dosage Forms Containing BCS Class I Drugs: Comparative Assessment of Metronidazole, Zidovudine, and Amoxicillin Versus Relevant Comparator Pharmaceutical Products in South Africa and India

Cited by 34 publications

References 5 publications

Application of Biowaiver Methodology for a Post-Marketing Study of Generic and Brand Name Metronidazole Tablets

Application of Biowaiver Methodology for a Post-Marketing Study of Generic and Brand Name Metronidazole Tablets

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In Vitro Dissolution Similarity as a Surrogate for In Vivo Bioavailability and Therapeutic Equivalence

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