Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Metronidazole

Rediguieri, Camila Fracalossi; Porta, Valentina; Nunes, Diana S. G; Nunes, Taina M.; Junginger, Hans E.; Kopp, Sabine; Midha, K. K.; Shah, Vinod P.; Stavchansky, Salomon A; Dressman, Jennifer B.; Barends, D. M.

doi:10.1002/jps.22409

Cited by 57 publications

(36 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Otherwise, the slow rate of metronidazole absorption from tablets was reported to be associated with the slow dissolution in the USP basket apparatus at 100 rpm using 0.1 N hydrochloric acids as dissolution medium [33]. Other researchers have reported variations in absorption, lack of bioequivalence, and ineffective treatment due to low drug levels [34].…”

Section: Dissolution Profilesmentioning

confidence: 99%

In Vitro Release Studies of Carbamazepine Tablets and Benzoyl Metronidazole Suspensions Using the Flow-Through Cell Apparatus and Simulated Gastrointestinal Fluids

2017

View full text Add to dashboard Cite

Objective: To characterize the in vitro release of carbamazepine tablets and benzoyl metronidazole suspensions using the flow-through cell apparatus and simulated gastrointestinal fluids.Methods: Tegretol ® tablets, Flagyl ® suspension, and generic formulations of each were tested. Release studies were performed using an automated flow-through cell apparatus. Simulated gastric fluid (with and without pepsin) and simulated intestinal fluid (without pancreatin) at 16 ml/min and fasted state simulated intestinal fluid at 8 ml/min, all at 37.0±0.5 °C, were used as dissolution media. The quantity of dissolved carbamazepine and benzoyl metronidazole was determined at 5-min intervals until 60 min at 285 and 278 nm, respectively. Percentage dissolved at 60 min, mean dissolution time, dissolution efficiency values, and t10%, t25%, t50% and t63.2% were calculated. Mean values for all parameters were compared between the reference and generic formulations using Studentʼs t-test. Dissolution data were fitted to different kinetic models.Results: Simulated gastric fluid without pepsin showed no discriminative capability for carbamazepine tablets. Significant differences were observed between the reference and generic formulations for almost all parameters (*P<0.05). In some cases, the logistic model best described the in vitro release of both drugs. Conclusion:Using an apparatus and media that best simulates the gastrointestinal environment, we identified differences in the rate and extent of dissolution of both drugs that could help to optimise the design of interchangeable formulations. Based on the physicochemical characteristics of carbamazepine and benzoyl metronidazole and the conditions in which the formulations were tested, these differences could be of clinical relevance.

show abstract

Section: Dissolution Profilesmentioning

confidence: 99%

In Vitro Release Studies of Carbamazepine Tablets and Benzoyl Metronidazole Suspensions Using the Flow-Through Cell Apparatus and Simulated Gastrointestinal Fluids

2017

View full text Add to dashboard Cite

show abstract

“…All the products, except Gendazole F®, achieved the SGF the USP release requirement. Rediguieri et al indicated that certain excipients such as sorbitol, sodium lauryl sulfate, and propylene glycol has been known to alter the bioavailability of some metronidazole formulations [30]. Magnesium stearate, which was present in some of the products investigated, can also affect the dissolution profile of the finished products [31].…”

Section: Metronidazolementioning

confidence: 99%

Investigating the Dissolution Profiles of Amoxicillin, Metronidazole, and Zidovudine Formulations used in Trinidad and Tobago, West Indies

2014

View full text Add to dashboard Cite

Abstract. Trinidad and Tobago is a twin-island Republic in the Caribbean and like many developing countries, it has included generic drugs on the national drug formulary to decrease the financial burden of pharmaceutical medications. However, to ensure that medications received by patients are beneficial, generic drugs need to be interchangeable with the innovator which has demonstrated safety, efficacy, and quality. The objective of the study was to compare the dissolution profiles and weight variations for different formulations of amoxicillin, metronidazole, and zidovudine that are on the national drug formulary and marketed in Trinidad and Tobago. All the products investigated are categorized as class 1 drugs according to the Biopharmaceutics Classification System (BCS) and the dissolution profiles were assessed according to the World Health Organization (WHO) criteria for interchangeability between products. The similarity factor, f 2 , was used to determine sameness between the products. No generic formulation was found to be similar to Amoxil® 500-mg capsules. The two generic products for metronidazole 200-mg tablets demonstrated more than 85% drug release within 15 min in all three of the buffers; however, their 400-mg counterparts did not fulfill this requirement. The zidovudine 300-mg tablet complied with the requirements in buffer pH 4.5 and simulated gastric fluid (SGF) but not for simulated intestinal fluid (SIF). Some Class 1 pharmaceutical formulations may possess the same active ingredient and amount of drug but may show significant differences to in vitro equivalence requirements. Nevertheless, the dissolution process is suitable to detect these variations.

show abstract

“…Because of such and other positive bioequivalent results in in-vivo studies, metronidazole tablets are suggested to be classified in the biowaiver class to the biopharmaceutics classification system of class I for immediate oral release solid oral dosage forms. 18 . Here results in our in vitro dissolution studies also support the immediate release of the active ingredient in the tablets except for one brand which is film coated in which the coating might interfere in its disintegration and dissolution properties of the product.…”

Section: Fig 2: Time Dependent Dissolution Profile Of Different Branmentioning

confidence: 99%

Untitled

2013

IJPSR

View full text Add to dashboard Cite

In this study, five different products of each metronidazole tablets and benzoate salt oral suspensions were purchased from the different retail outlets in the local market of Addis Ababa and analyzed using official methods (Pharmacopoeial methods of USP/BP/IP) by employing HPLC for the tablet dosage forms and nonaqueous titration with potentiometric end point for the suspensions. The assay results showed that all brand and generic products of metronidazole tablets and metronidazole benzoate oral suspensions met the USP and the IP specifications, respectively. Furthermore, all the tablets analyzed have passed the hardness, friability and weight variation tests. All tablets except metrogyl passed the disintegration time test and dissolution rate test specifications of BP/USP. In addition, different brands and a generic product of metronidazole benzoate oral suspensions were evaluated by determining their physical stability with respect to the two useful parameters, sedimentation volume and Viscosity. Amrizole has relatively moderate viscosity (728.0 ± 0.12 cP), which may cause good pourability of the suspension with a sedimentation value of 1 (acceptable and stable suspension). On the other hand Camezol has low viscosity (9.2 ± 0.40 cP) and sedimentation Value (0.10) that may cause faster sedimentation of the particles of the suspension. This study showed the importance of post marketing surveillance for the drugs imported and distributed in the country, Ethiopia.

show abstract

Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Metronidazole

Cited by 57 publications

References 26 publications

In Vitro Release Studies of Carbamazepine Tablets and Benzoyl Metronidazole Suspensions Using the Flow-Through Cell Apparatus and Simulated Gastrointestinal Fluids

In Vitro Release Studies of Carbamazepine Tablets and Benzoyl Metronidazole Suspensions Using the Flow-Through Cell Apparatus and Simulated Gastrointestinal Fluids

Investigating the Dissolution Profiles of Amoxicillin, Metronidazole, and Zidovudine Formulations used in Trinidad and Tobago, West Indies

Untitled

Contact Info

Product

Resources

About