RESUMO
OBJECTIVE: To mask the bitterness of Chlorpheniramine Maleate via encapsulating drug into Eudragit EPO microparticles, and then incorporate these microparticles into orally disintegrating films (ODF) and orally disintegrating tablets (ODT) for pediatric uses. METHODS: Spray drying of water-in-oil emulsion was utilized to encapsulate Chlorpheniramine Maleate into Eudragit EPO microparticles. Based on an orthogonal experimental design L9 (3(3)), polynomial regression models were developed to evaluate correlation between microparticle properties (encapsulation efficiency and drug release) and variables (X1: weight ratio of polymer to drug, X2: volume ratio of oil to water and X3: Q-flow of spray dryer). ODF and ODT formulations were evaluated including weight variation, content uniformity, tensile strength, disintegration time, friability and dissolution profiles. The bitterness taste test was evaluated in 10 adult volunteers. RESULTS AND DISCUSSION: From polynomial regression analysis, the best values of variables leading to the optimized microparticles were X1 = 10, X2 = 3 and X3 = 45. The optimized microparticles were incorporated into ODF and ODT with satisfactory weight and drug content uniformity, and acceptable physical strength. Both dosage forms disintegrated immediately (less than 40 s) in simulated saliva solutions. The outcome of taste-masking test indicated that microparticles alleviated drug bitterness significantly; bitterness was not discernible with microparticles incorporated in ODT, whereas only slight bitterness was detected from microparticles incorporated into ODF. CONCLUSION: Both ODF and ODT are shown to be suitable vehicles for taste masked Chlorpheniramine Maleate microparticles with potential for pediatric uses.
Assuntos
Clorfeniramina/administração & dosagem , Portadores de Fármacos/química , Ácidos Polimetacrílicos/química , Paladar , Administração Oral , Adulto , Fenômenos Químicos , Química Farmacêutica , Criança , Clorfeniramina/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Humanos , Modelos Biológicos , Tamanho da Partícula , Análise de Regressão , Saliva/química , Solubilidade , Comprimidos , Resistência à Tração , LínguaRESUMO
OBJECTIVE: The purpose of this study is to evaluate the influence of sodium iodide, sodium chloride and sodium sulfate on the formation efficiency of sulfamerazine nanocrystals by wet ball milling. METHODS: Sulfamerazine was milled using zirconium oxide beads in a solution containing polyvinylpyrrolidone (PVP) and a sodium salt (iodide, chloride or sulfate). Particle size distributions were evaluated by light diffraction before and after milling. High-performance liquid chromatography was utilized to determine the amount of PVP adsorbed onto sulfamerazine surface. Lyophilized nanocrystals were further characterized by differential scanning calorimetry and dissolution testing. RESULTS: Sulfate ion had more profound effect on reducing particle size via milling than iodide or chloride. We linked our findings to Hofmeister ion series, which indicates that sulfate ions tends to break the water structure, increases the surface tension and lowers the solubility of hydrocarbons in water. We hypothesized that the addition of sulfate ions dehydrated the PVP molecules and enhanced its adsorption onto the sulfamerazine particle surfaces. Consequently, the adsorbed PVP helped to stabilize of the nanosuspension. The nanocrystals that were obtained from the lyophilized milled suspensions exhibited a notable increase in dissolution rate. CONCLUSION: The addition of sodium sulfate enhanced the formation efficiency of sulfamerazine nanocrystals.