RESUMO
BACKGROUND: Oral suspensions are heterogeneous disperse systems, and the particle size distribution, crystalline form of the dispersed solid, and composition of the formulation can be listed as parameters that control the drug dissolution rate and its bioavailability. OBJECTIVE: The aim of this work was to develop a discriminative dissolution test, which, in association with in silico methodologies, can make it possible to safely anticipate bioavailability problems. METHODS: Nimesulide and ibuprofen (BCS class II) and cephalexin (BCS class I) oral suspensions were studied. Previously, solid-state structure and particle size in active pharmaceutical ingredients were characterized and the impact of differences on solubility was evaluated for the choice of discriminative medium. Afterwards, particle size distribution (0.1 to 360 µm), dissolution profile, and in vitro permeability in Caco-2 cell of commercial suspensions, were determined. These parameters were used as input for the establishment of the in vitro-in vivo correlation (IVIVC) for the suspensions using the GastroPlus™ with Wagner-Nelson and Loo- Riegelmann deconvolution approach. RESULTS: The predicted/observed pharmacokinetic model showed good correlation coefficients (r) of 0.960, 0.950, and 0.901, respectively. The IVIVC was established for one nimesulide and two ibuprofen suspensions with r between 0.956 and 0.932, and the percent prediction error (%PE) did not exceed 15%. CONCLUSION: In this work, we have performed a complete study combining in vitro/in silico approaches with the aim of anticipating the safety and efficacy of oral pharmaceutical suspensions in order to provide a regulatory tool for this category of products in a faster and more economical way.
Assuntos
Ibuprofeno , Sulfonamidas , Humanos , Disponibilidade Biológica , Ibuprofeno/química , Ibuprofeno/farmacocinética , Células CACO-2 , Solubilidade , SuspensõesRESUMO
OBJECTIVES: The objective of this study was to evaluate the compatibility of 10 commonly used active pharmaceutical ingredients (APIs) compounded in oral suspensions using a globally available suspending vehicle (SyrSpend SF PH4 liquid): caffeine 10.0â mg/mL, carvedilol 1.0â mg/mL, clomipramine hydrochloride 5.0â mg/mL, folic acid 1.0â mg/mL, hydrochlorothiazide 5.0â mg/mL, loperamide hydrochloride 1.0â mg/mL, methotrexate 2.5â mg/mL, nadolol 10.0â mg/mL, naltrexone hydrochloride 1.0â mg/mL and pentoxifylline 20.0â mg/mL, stored at both controlled refrigerated (2-8°C) and room (20-25°C) temperature. METHODS: Compatibility was assessed by measuring the per cent recovery at different time points throughout a 90-day period. Quantification of the APIs was performed by high performance liquid chromatography (HPLC-UV) using a stability-indicating method. RESULTS: Methods were adequately validated. Forced degradation studies showed that at least one parameter influenced the stability of the APIs. All suspensions were assayed and showed API contents of between 90% and 110% over 90â days. DISCUSSION: Given the percentage of recovery of the APIs within the suspensions, the expiration date of the final products (API+vehicle) was found to be at least 90â days for all suspensions, for both controlled refrigerated and room temperature. CONCLUSIONS: The results suggest that SyrSpend SF PH4 liquid is a stable suspending vehicle for compounding APIs from different pharmacological classes.
RESUMO
The present study describes the development and validation of an in vitro dissolution method for evaluation to release diclofenac potassium in oral suspension. The dissolution test was developed and validated according to international guidelines. Parameters like linearity, specificity, precision and accuracy were evaluated, as well as the influence of rotation speed and surfactant concentration on the medium. After selecting the best conditions, the method was validated using apparatus 2 (paddle), 50-rpm rotation speed, 900 mL of water with 0.3% sodium lauryl sulfate (SLS) as dissolution medium at 37.0 ± 0.5°C. Samples were analyzed using the HPLC-UV (PDA) method. The results obtained were satisfactory for the parameters evaluated. The method developed may be useful in routine quality control for pharmaceutical industries that produce oral suspensions containing diclofenac potassium.
O presente estudo descreve o desenvolvimento e validação de um método de dissolução in vitro para avaliação da liberação de diclofenaco potássico suspensão oral. O teste de dissolução foi desenvolvido e validado de acordo com as diretrizes internacionais. Parâmetros como linearidade, especificidade, precisão e exatidão foram avaliados, bem como a influência da velocidade de rotação e a concentração de tensoativono meio. Depois de selecionar as melhores condições, o método foi validado usando o aparato 2 (pás), velocidade de rotação de 50 rpm, 900 mL de água com 0,3% de lauril sulfato de sódio (LSS) como meio de dissolução a 37,0 ± 0,5 ºC. As amostras foram analisadas pelo método de CLAE-UV (PDA). Os resultados obtidos foram satisfatórios para os parâmetros avaliados. O método desenvolvido pode ser útil na rotina de controle de qualidade para as indústrias farmacêuticas que produzem suspensões orais contendo diclofenaco potássico.