Determination of Simultaneous Sulfamethoxazole and Trimethoprim by Ultraviolet Spectrophotometry With Mean Centering of Ratio Spectra

Objective: To estimate plasma concentrations-time profiles of Sulfamethoxazole (SMZ) and Trimethoprim (TMP) from fixed-dose combination formulations through in vitro data of dissolution media of physiological relevance and a convolution model. Methods: Dissolution profiles of SMZ/TMP tablets (400/80 mg) were obtained with USP paddle apparatus at 100 rpm and 900 ml of 0.1 N HCl, pH 4.5 acetate buffer, and pH 6.8 phosphate buffer. The reference drug product and two generic formulations were tested. Drugs were quantified by a derivative method. Dissolution profiles were compared with model-dependent and independent methods. SMZ/TMP plasma levels were simulated with dissolution data and published in vivo information. Percent of prediction error (PE) for peak plasma concentration (Cmax) and area under the curve from zero time to infinity (AUC0-inf) at each condition were calculated. Results: In all used conditions, similar dissolution profiles were found excepting for TMP at pH 1.2 (f2<50). The in vitro release performance for reference and generic formulations was explained by the Weibull function only for SMZ at pH 6.8 and TMP at pH 4.5. Values of PE>19% for both generic formulations were found with TMP at pH 1.2. Conclusion: Significant differences in TMP dissolution profiles of generic formulations at pH 1.2 reflect the subsequent differences found in predicted Cmax and AUC0-inf.

Section: In Vitro Release Studiesmentioning

confidence: 99%

Prediction of Sulfamethoxazole and Trimethoprim Plasma Levels From Tablets and Dissolution Media of Physiological Relevance

RIOS-RODRIGUEZ,

REYES-RAMIREZ,

RUIZ-SEGURA

et al. 2024

“…Various studies on the development of Spectrophotometry methods have been published as examples: UV spectrophotometry methods for simultaneous estimation, Double Divisor Spectra derivative spectrophotometry ratio, and MCR method [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Assays of Metformin HCL and Glibenclamide Mixture Using Two Analytical Methods of Spectrophotometry

Bachri

2019

Objective: Area Under Curve method (AUC) and the Multiple Wavelength Spectrophotometric (MWS) method are practice and simple methods for simultaneous assays of Metformin HCl and Glibenclamide on the tablet dosage form. Methods: The AUC method is measured for the absorption spectrum with a concentration 4 mg/l Metformin HCl by calculating the area spectrum at wavelength 230-240 nm and the absorption spectrum with a concentration 8.7 mg/l Glibenclamide by calculating the area at wavelength 225-235 nm. The MWS by determining the absorption spectrum and the five wavelength points for the absorption value at 225 nm, 229.4 nm, 236.6 nm, 233 nm, and 243 nm and calculated using matrix operations. Results: The validation test of the AUC method for Metformin HCl obtained accuracy = 99.35%, linearity = 0.9881, precision = 0.39%, LOD = 0.4459 mg/l. LOQ = 1.4864 mg/l and for Glibenclamide obtained accuracy = 100.79%, linearity = 0.9993, precision = 0.65%, LOD=0.4372 mg/l, LOQ = 1.4072 mg/l and the MWS method for Metformin HCl obtained accuracy = 100.76%, linearity 0.9949, precision = 0.65%, LOD = 0.9103 mg/l, LOQ = 3.0431 mg/l, and for Glibenclamide with accuracy = 100.07%, linearity = 0.9993. precision = 0.36%, LOD = 0.9205 mg/l. LOQ = 3.0431 mg/l , and appropriate the requirements of ICH guidelines. Conclusion: These Methods successively applied to determine of Metformin HCl and Glibenclamide mixture in tablet dosage form and fulfill the validation requirements.

Estimation of in Vivo Performance of Sulfamethoxazole and Trimethoprim From Oral Suspensions Using in Vitro Release Data From a Mini Paddle Apparatus

RUIZ-SEGURA,

RIOS-RODRÍGUEZ,

REYES-RAMÍREZ

et al. 2024

Objective: To estimate plasma concentrations-time profiles of sulfamethoxazole (SMZ) and trimethoprim (TMP) from oral pediatric suspensions through in vitro data generated with a mini paddle apparatus and dissolution media of physiological relevance. Post-marketing evaluation of pediatric formulations is always necessary. Methods: Dissolution profiles of SMZ/TMP were obtained with a mini paddle apparatus at 100 rpm and 200 ml of 0.1 N HCl (pH 1.2), pH 4.5 acetate buffer, and pH 6.8 phosphate buffer. The reference and three multi-source pediatric formulations were tested. Drugs were quantified by a UV derivative method. Dissolution profiles were compared with model-independent and model-dependent methods. Plasma levels were estimated with dissolution data and published in vivo information. Percent of prediction error (%PE) for Cmax and AUC0-inf at each condition was calculated. Results: In all conditions, similar dissolution profiles were found excepting for TMP of C drug product at pH 1.2 (f2<50). With model-independent comparisons significant differences in in vitro release performance of SMZ and TMP from all multi-source formulations were found (*P<0.05). When comparing the hypothetical Cmax and AUC0-inf of both drugs with in vivo data PE<15% were found only with reference and one formulation at pH 1.2. Conclusion: The mini paddle apparatus and dissolution media of pH 1.2 were the best conditions to estimate in vivo plasma concentrations of SMZ and TMP from reference. These settings seem adequate to evaluate in vitro performance of multi-source formulations. It is necessary to carried out human studies with the used fixed-dose combination formulations to correlate in vitro/in vivo data.