Dissolution Behavior of Carbamazepine Suspensions Using the Usp Dissolution Apparatus 2 and the Flow-Through Cell Method with Simulated Gi Fluids (original) (raw)
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Saudi Pharmaceutical Journal, 2014
Dissolution profiles of four carbamazepine immediate-release generic products (200 mg tablets) and the reference product TegretolÒ were evaluated using the USP paddles method and an alternative method with the flow-through cell system, USP Apparatus 4. Under official conditions all products met the Q specification, dissolution profiles of generic products were similar to the dissolution profile of the reference product (f 2 > 50) and model-independent parameters showed non significant differences to the reference product except mean dissolution time for product A (p < 0.05). On the other hand, when the flow-through cell system was used, none of the products met the pharmacopeial specification at 15 min and product A did not reach dissolution criteria at 60 min, dissolution profiles of all generic products were not similar to the reference product profile (f 2 < 50) and all model-independent parameters showed significant differences compared to the reference product (p < 0.05). Weibull's model was more useful for adjusting the dissolution data of all products in both USP apparatuses and Td values showed significant differences compared to the reference product (p < 0.05) when USP Apparatus 4 was used. These results indicate that the proposed method, using the flow-through cell system, is more discriminative in evaluating both, rate and extent of carbamazepine dissolution process from immediate-release generic products. ª 2013 Production and hosting by Elsevier B.V. on behalf of King Saud University.
Pharmaceutics
The aim of the present study was to bring additional evidence regarding a biopredictive dissolution medium containing 1% sodium lauryl sulphate (SLS) to predict the in vivo behavior of carbamazepine (CBZ) products. Twelve healthy volunteers took one immediate release (IR) dose of either test and reference formulations in a bioequivalence study (BE). Dissolution profiles were carried-out using the medium. Level A in vitro–in vivo correlations (IVIVC) were established using both one-step and two-step approaches as well as exploring the time-scaling approach to account for the differences in dissolution rate in vitro versus in vivo. A detailed step by step calculation was provided to clearly illustrate all the procedures. The results show additional evidence that the medium containing 1% SLS can be classified as a universal biopredictive dissolution tool, and that both of the approaches used to develop the IVIVC (one and two-steps) provide good in vivo predictability. Therefore, this b...
Investigation of intrinsic dissolution behavior of different carbamazepine samples
International Journal of Pharmaceutics, 2010
The aim of the present study was to investigate the effect of the variability of commercially available carbamazepine (CBZ) samples on the intrinsic dissolution behavior in order to recommend a strategy to maintain product quality by monitoring the variability of critical parameters of the bulk drug.
Asian Journal of Pharmaceutics, 2008
T he effect of HPMC on solubility and dissolution of carbamazepine form III (CBZ) was investigated in 50% w/w of CBZ form III in HPMC solid dispersion and physical mixture. Powdered samples of CBZ form III, physical mixture, and solid dispersion were characterized for thermal behavior (DSC), crystallinity (PXRD), and compatibility (FT-IR). Solubility and dissolution studies were carried out in different simulated gastrointestinal fluids and de-ionized water. Solubility studies in simulated gastric fluid (SGF) revealed that acidic pH favors formation of CBZ dihydrate. Triton X 100 in blank fast-state simulated gastric fluid (FaSSGF) prevents the formation of CBZ dihydrate in acidic pH. A maximum solubility of 268.77 µg/mL was achieved with fed-state simulated intestinal fluid (FeSSIF). Correlation between solubility and pH could not be established. Both solubility and dissolution studies revealed that HPMC had a profound effect of enhancement of solubility and dissolution of CBZ form III in both physical mixtures and solid dispersions. HPMC prevents the formation of CBZ dihydrate and thereby improves the solubility and dissolution. This was further correlated with results obtained from DSC and XRD. There was no drastic difference in solubility and dissolution of CBZ form III with different media. It was observed that there was no existing relationship between solubility and dissolution of CBZ form III in different media.
Molecular Pharmaceutics, 2009
The aim of the present study was to use gastrointestinal simulation technology and in vitro-in vivo correlation (IVIVC) as tools to investigate a possible extension of biowaiver criteria to BCS class II drugs using carbamazepine (CBZ) as a candidate compound. Gastrointestinal simulation based on the advanced compartmental absorption and transit model implemented in GastroPlus was used. Actual in vitro and in vivo data generated in CBZ bioequivalence studies were used for correlation purposes. The simulated plasma profile, based on the CBZ physicochemical and pharmacokinetic properties, was almost identical with that observed in vivo. Parameter sensitivity analysis (PSA) indicated that the percent of drug absorbed is relatively insensitive to the variation of the input parameters. Additionally, plasma concentration-time profiles were simulated based on dissolution profiles observed under the different experimental conditions. Regardless of the differences observed in vitro, the predicted pharmacokinetic profiles were similar in the extent of drug exposure (AUC) while there were certain differences in parameters defining the drug absorption rate (C max , t max ). High level A IVIVC was established for the pooled data set (r ) 0.9624), indicating that 1% SLS may be considered as the universal biorelevant dissolution medium for both the IR and CR CBZ tablets. The proposed methodology involving gastrointestinal simulation technology and IVIVC suggests that there is a rationale for considering CBZ biowaiver extension and introduction of the wider dissolution specifications for CBZ immediate release tablets.
In Vitro Absorption Study of Carbamazepine Solid Dispersion Using Everted Gut Sac Method
INDONESIAN JOURNAL OF PHARMACY, 2013
The oral Bioavailability of BCS (Bio Pharmaceutical Classification System) class II drug with poor solubility and reasonable permeability is limited by drug dissolution. In order to improve the aqueous solubility of the drug and dissolution of the drug, the solid dispersion was prepared and evaluated for its absorption in intestine using modified everted gut sac method. The solid dispersion of carbamezepine (CBZ) was prepared using polaxomer and guargum by kneading method. The CBZ and CBZ-SD (Solid Disposisi) shows 2.329% and 3.948% drug absorption, respectively. The data show that solid dispersion increase the absorption of the CBZ in CBZ-SD is more than 70% in comparison to pure CBZ. The increase in CBZ solubility of the SD could be attributed to several factors such as improved wettability, local solubilization, drug particle size reduction and crystalline or, interstitial solid solution reduction.
International Journal of Applied Pharmaceutics, 2017
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...
Formulation development and evaluation of Carbamazepine fast dissolving tablets
Background: The main objective of present research work is to formulate the Carbamazepine Fast Dissoving tablets. Carbamazepine, an antiepileptic, belongs to BCS Class-II and used to control some types of seizures in the treatment of epilepsy and Neuropathic Pain by blocking use-dependent sodium channels. Methods: The Fast Dissoving tablets of Carbamazepine were prepared employing different concentrations of Crospovidone and Croscarmellose sodium in different combinations as a Sperdisintegrants by Direct Compression technique using 32 factorial design. The concentration of Crospovidone and Croscarmellose sodium was selected as independent variables, X1 and X2 respectively whereas, wetting time, Disintegration time, t50% ,t90%were selected as dependent variables. Results and Discussion: Totally nine formulations were designed and are evaluated for hardness, friability, thickness, Assay, Wetting time, Disintegration time, In-vitro drug release. From the Results concluded that all the formulation were found to be with in the Pharmacopoeial limits and the In-vitro dissolution profiles of all formulations were fitted in to different Kinetic models, the statistical parameters like intercept (a), slope (b) & regression coefficient (r) were calculated. Polynomial equations were developed for Wetting time, Disintegration time, t50%, t90%. Validity of developed polynomial equations were verified by designing 2 check point formulations (C1, C2). According to SUPAC guidelines the formulation (F5) containing combination of 9.375% Crospovidone and 9.375% Croscarmellose, is the most similar formulation (similarity factor f2=82.675, dissimilarity factor f1= 2.049 & No significant difference, t= 0.041) to marketed product (TEGRETOL-100). Conclusion: The selected formulation (F5) follows First order, Higuchi’s kinetics, mechanism of drug release was found to be Non-Fickian Diffusion (n= 0.665).
FORMULATION DEVELOPMENT AND EVALUATION OF FAST DISSOLVING TABLET OF CARBAMAZEPINE
To obviate the problem of dysphasia & to improve patient compliance, FDT have gained considerable attention over the conventional dosage form such as tablet & capsule. Carbamazepine is dibenzapine derivative with structure resembling that of tricyclic antidepresent,is used in epilepsy. The major problem of this drug is very low solubility in biological fluid & poor bioavailability after oral administration. The present work focus on the effect of superdisintegrents (such as crosspovidone, sodium starch glycolate & pregelatinized starch.) on wetting time,disintegrating time,drug content, in vitro drug release, stability parameter studied. No chemical interaction between drug & excipient was confirmed by DSC & FTIR studies. Among all formulation F was considered best. The result concluded that FDT of poorly soluble drug carbamazepine, showing enhanced dissolution, will lead to improved bioavailability, improved effectiveness& hence better patience compliance.