scholarly journals DISSOLUTION BEHAVIOR OF CARBAMAZEPINE SUSPENSIONS USING THE USP DISSOLUTION APPARATUS 2 AND THE FLOW-THROUGH CELL METHOD WITH SIMULATED GI FLUIDS

2017 ◽  
Vol 9 (10) ◽  
pp. 111
Author(s):  
Jose Raul Medina ◽  
Erik Aguilar ◽  
Marcela Hurtado
Keyword(s):  
Laminar Flow ◽  
Simulated Gastric Fluid ◽  
Cell Method ◽  
Drug Products ◽  
Flow Through ◽  
Model Independent ◽  
Dissolution Apparatus ◽  
Usp Apparatus ◽  
Usp Apparatus 2 ◽  
Independent Parameters

Objective: To characterize the dissolution behaviour of carbamazepine generic suspensions using the USP Dissolution Apparatus 2 and the flow-through cell method with simulated gastrointestinal fluids as dissolution media.Methods: Tegretol® suspension and two generic formulations were tested. Dissolution studies were performed using the USP Apparatus 2 (75 rpm and 900 ml of dissolution medium) and the flow-through cell method (laminar flow at 16 ml/min). Simulated gastric fluid (SGF) (with and without pepsin) and simulated intestinal fluid (SIF) (without pancreatin) at 37.0±0.5 °C, was used as dissolution media. The quantity of dissolved carbamazepine was determined at 5 min intervals until reaching 60 min, at 285 nm. Percentage dissolved at 60 min, mean dissolution time, dissolution efficiency values (model-independent parameters), as well as t50% and t63.2% were calculated (model-dependent parameters). Values for all parameters were compared between the reference and generic formulations using one-way analysis of variance (ANOVA) following a Dunnett’s multiple comparison test. Dissolution data were also fitted to different fit models.Results: Since the first sampling time, the reference product had reached 100% of drug dissolved, which was determined using USP Apparatus 2. Nevertheless, significant differences in the three model-independent parameters of generic products were found (*P<0.05). Dissolution data obtained with the paddle apparatus were fitted to different kinetic equations; however, using the flow-through cell method and SIF without pancreatin, the three drug products were fitted to the same kinetic model (Gompertz). With ANOVA-based comparisons and the flow-through cell method, significant differences were found in dissolution data of generic product A versus reference at all sampling times (*P<0.05). The flow-through cell method and SGF with pepsin were the best options to discriminate among dissolution profiles.Conclusion: The flow-through cell method seems to be an adequate dissolution apparatus to characterize in vitrodissolution performance of Class II drugs manufactured as suspensions. For carbamazepine suspensions, SGF and laminar flow at 16 ml/min were the most appropriate conditions to discriminate among generic formulations. Given the physicochemical characteristics of carbamazepine and the environment in which the drug products were tested, these differences could be of clinical relevance. 

scholarly journals INFLUENCE OF DOSE AND USP DISSOLUTION APPARATUS IN THE RELEASE PERFORMANCE OF REFERENCE TABLETS: PROPRANOLOL-HCl AND RANITIDINE-HCl CASES

2019 ◽  
pp. 164-170
Author(s):  
JOSE RAUL MEDINA-LOPEZ ◽  
LUIS ANTONIO CEDILLO-DIAZ ◽  
MARCELA HURTADO
Keyword(s):  
In Vitro Dissolution ◽  
Dissolution Time ◽  
Reference Drug ◽  
Cell Method ◽  
Drug Products ◽  
Propranolol Hcl ◽  
Flow Through ◽  
Dissolution Apparatus ◽  
Paddle Apparatus

Objective: Due to quality of generic formulations depends on available information of reference drug products the aim of this work was to perform an in vitro dissolution study of two doses of propranolol-HCl and ranitidine-HCl reference tablets using USP basket or paddle apparatus and flow-through cell method. Methods: Two doses of propranolol-HCl (10-mg and 80-mg) and ranitidine-HCl (150-mg and 300-mg) of Mexican reference products were used. Dissolution profiles of propranolol-HCl were obtained with USP basket apparatus at 100 rpm and 1000 ml of 1% hydrochloric acid. Profiles of ranitidine-HCl were determined with USP paddle apparatus at 50 rpm and 900 ml of distilled water. All formulations were also studied with the flow-through cell method using laminar flow at 16 ml/min. Dissolution profiles were compared by model-independent (f2 similarity factor, mean dissolution time and dissolution efficiency) and model-dependent methods (dissolution data adjusted to some mathematical equations). Time data, derived from these adjustments, as t50%, t63.25%, and t85% were used to compare dissolution profiles. Results: With all approaches used and being high solubility drugs significant differences were found between low and high doses and between USP dissolution apparatuses (*P<0.05). Conclusion: In vitro dissolution performance of two doses of propranolol-HCl and ranitidine-HCl was not expected. Considering the same USP dissolution apparatus, the reference tablets did not allow the simultaneous release of the used doses. The results could be of interest for pharmaceutical laboratories or health authorities that classify some drug products as a reference to be used in dissolution and bioequivalence studies.

scholarly journals COMPARISON OF THE USP APPARATUS 2 AND 4 FOR TESTING THE IN VITRO RELEASE PERFORMANCE OF IBUPROFEN GENERIC SUSPENSIONS

2017 ◽  
Vol 9 (4) ◽  
pp. 90 ◽  
Author(s):  
Jose Raul Medina ◽  
Mariel Cortes ◽  
Erik Romo
Keyword(s):  
In Vitro Release ◽  
Generic Product ◽  
Dissolution Profile ◽  
Drug Products ◽  
Flow Through ◽  
Usp Apparatus 4 ◽  
Usp Apparatus ◽  
Usp Apparatus 2 ◽  
Vitro Release

Objective: The aim of this study was the comparison of the in vitro release performance of ibuprofen generic suspensions and reference, based on the hydrodynamic environment generated by the flow-through cell method (USP Apparatus 4). Results were compared with those obtained by the use of the USP Apparatus 2.Methods: The Advil® suspension (2 g/100 ml) and two generic formulations with the same dose were tested. Dissolution studies were carried out using a USP Apparatus 4 Sotax CE6 with 22.6 mm cells, laminar flow at 16 ml/min, and pH 7.2 phosphate buffer at 37.0±0.5 °C as dissolution medium. Ibuprofen was quantified spectrophotometrically at 222 nm. The in vitro release of the three drug products were studied using the USP Apparatus 2. The dissolution profiles of generic products were compared with the reference by model-independent, model-dependent, and analysis of variance (ANOVA)-based comparisons.Results: The dissolution profile of the generic product A was similar to the dissolution profile of reference, only with the use of the USP Apparatus 4. The f2 similarity factor was>50 and no significant differences were found with dissolution efficiency data (*P>0.05). Similar results were found with the comparison of t50% and t63.2% values. Similar dissolution profiles between generic product A and reference were also found with ANOVA-based comparisons.Conclusion: The flow-through cell method was adequate for study the in vitro release of ibuprofen suspensions. It is necessary to evaluate the in vivoperformance of the drug products used in order to estimate the predictability of the proposed methodology. 

scholarly journals Instrumentation of Flow-Through USP IV Dissolution Apparatus to Assess Poorly Soluble Basic Drug Products: a Technical Note

2015 ◽  
Vol 17 (5) ◽  
pp. 1261-1266 ◽  
Author(s):  
Alice Paprskářová ◽  
Petra Možná ◽  
Enoche F. Oga ◽  
Abdelbary Elhissi ◽  
Mohamed A. Alhnan
Keyword(s):  
Technical Note ◽  
Basic Drug ◽  
Drug Products ◽  
Poorly Soluble ◽  
Flow Through ◽  
Dissolution Apparatus

scholarly journals DISSOLUTION PERFORMANCE OF MELOXICAM FORMULATIONS UNDER HYDRODYNAMICS OF USP PADDLE APPARATUS AND FLOW-THROUGH CELL METHOD

2019 ◽  
pp. 182-188
Author(s):  
OSE RAUL MEDINA-LOPEZ ◽  
JOSE ANGEL OROZCO-JUAREZ ◽  
MARCELA HURTADO
Keyword(s):  
In Vitro Dissolution ◽  
Dissolution Time ◽  
Weibull Function ◽  
Cell Method ◽  
Drug Products ◽  
Poorly Soluble ◽  
Flow Through ◽  
Dissolution Efficiency ◽  
Paddle Apparatus

Objective: To study the in vitro dissolution performance of four generic formulations of the poorly soluble drug meloxicam and the reference under hydrodynamic environments generated by flow-through cell method and USP paddle apparatus (pharmacopeial test). Methods: Dissolution method was validated according to ICH guidelines. Dissolution profiles were carried out with an automated flow-through cell apparatus (laminar flow at 16 ml/min with 22.6 mm cells) and USP paddle apparatus at 75 rpm. Phosphate buffer pH 7.5 at 37.0±0.5 °C was used as dissolution medium. Spectrophotometric determination of drug at 362 nm was carried out during 30 min. Dissolution profiles were compared with model-dependent and-independent methods. Results: Practically, all generic formulations showed significant differences with the percentage of drug dissolved at 30 min, mean dissolution time and dissolution efficiency, when USP paddle apparatus was used (*P<0.05), while only two generic formulations were different to reference using flow-through cell method. After adjustment to different mathematical equations, Weibull function was the best model to describe meloxicam dissolution performance and significant differences were found with all drug products when USP paddle apparatus was used, while only one formulation was different with flow-through cell method. Conclusion: The study reveals the need to look for better dissolution schemes for meloxicam tablets since USP paddle apparatus may not reflect properly the in vitro dissolution performance of meloxicam generic formulations and reference.

scholarly journals IN VITRO EQUIVALENCE STUDY OF DIFFERENT DOSES OF CARBAMAZEPINE REFERENCE TABLETS USING USP APPARATUSES 2 AND 4

2019 ◽  
pp. 291-295
Author(s):  
JOSE RAUL MEDINA-LOPEZ ◽  
Luis Antonio Cedillo-Díaz ◽  
Marcela Hurtado
Keyword(s):  
High Dose ◽  
Local Market ◽  
Dissolution Medium ◽  
Usp 4 ◽  
Usp Apparatus 4 ◽  
Dissolution Apparatus ◽  
Usp Apparatus ◽  
Usp Apparatus 2

Objective: To perform an in vitro equivalence study of two doses of carbamazepine reference tablets sold in the local market under hydrodynamic conditions of USP Apparatus 4, a dissolution apparatus that better simulates the human gastrointestinal tract. Results were compared with dissolution official conditions using USP Apparatus 2. Methods: Dissolution profiles of both formulations were carried out with an automated USP Apparatus 2 at 75 rpm and 900 ml of dissolution medium. USP Apparatus 4 with laminar flow at 16 ml/min and 22.6 mm cells were used. 1% lauryl sulfate aqueous solution at 37.0±0.5 °C was used as dissolution medium. Spectrophotometric determination of drug at 285 nm was carried out during 60 min. Dissolution profiles were compared with model-independent and-dependent approaches. Results: When comparing dissolution profiles of low vs. high dose similar profiles were found (f2>50) in each dissolution apparatus, however, when the same dose was compared, USP 2 vs. USP 4, opposite results were obtained. Comparison of mean dissolution time and dissolution efficiency data corroborates these results. Weibull function was the best mathematical model that described the in vitro dissolution performance of carbamazepine. No significant differences were found in Td values (low vs. high dose) but opposite results were also found with USP 2 vs. USP 4. Conclusion: Equivalent dissolution performance of two doses of carbamazepine reference tablets were found in each USP dissolution apparatus. The main problem identified in this comparative study is the low dissolution rate and extent found with USP Apparatus 4. More research on this field is necessary for all available doses of reference drug products since the quality of generic formulations depends on the quality of references.

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