RESUMO
Lamotrigine a BCS class II drug used in treatment of epilepsy has several disadvantages when taken orally (first pass metabolism and increased Cmax). The aim of the study is to design core in cup (In lay) buccoadhesive tablets which aims for controlled, unidirectional release, increased patient compliance and decreased side effects. The present study involves the preparation of core in cup tablets containing release retarding polymers like sodium alginate, xanthan gum and HPMC E 15LV in core and HPMC K 15M in cup for mucoadhesion. L9 orthogonal array Taguchi design was constructed for the study. The dependent variable studied for L9 orthogonal array Taguchi runs include % drug release from which the formulation with highest S/N ratio was optimized. All the runs were evaluated for physical parameters, drug release, mucoadhesive studies and assay. L1, L2, L4 and L8 formulations showed controlled release for up-to 8 hours with good assay values. The model dependent kinetics showed zero order kinetics with super case II transport and Hixson Crowell mechanism which indicates unidirectional drug release.
RESUMO
The objective of the research was to formulate and evaluate selegiline hydrochloride loaded chitosan nanoparticles for the Parkinson's therapy in order to improve its therapeutic effect and reducing dosing frequency. Taguchi method of design of experiments (L9 orthogonal array) was used to get optimized formulation. The selegiline hydrochloride loaded chitosan nanoparticles (SHPs) were prepared by ionic gelation of chitosan with tripolyphosphate anions (TPP) and tween 80 as surfactant. The SHPs had a mean size of (303.39 ± 2.01) nm, a zeta potential of +32.50mV, and entrapment efficiency of SHPs was 86.200 ± 1.38%. The in vitro drug release of SHPs was evaluated in phosphate buffer saline (pH 5.5) using goat nasal mucosa and found to be 82.529% ± 1.308 up to 28 h. Release kinetics studies showed that the release of drug from nanoparticles was anomalous (non-fickian) diffusion indicating the drug release is controlled by more than one process i.e. superposition of both phenomenon, the diffusion controlled as well as swelling controlled release. SHPs showed good stability results as found during stability studies at different temperatures as mentioned in ICH guidelines. The results revealed that selegiline hydrochloride loaded chitosan nanoparticles are most suitable mode of delivery of drug for promising therapeutic action.
O objetivo da pesquisa foi formular e avaliar nanopartículas de quitosana contendo cloridrato de selegilina para terapia do Parkinson, a fim de melhorar o seu efeito terapêutico e reduzir a frequência de dosagem. Método de Taguchi, de planejamento experimental, (L9 matriz ortogonal) foi usado para obter a formulação otimizada. As nanopartículas de quitosana contendo cloridrato de selegilina (PCHs) foram preparadas por gelificação iônica de quitosana com ânions tripolifosfato (TPP) e Tween 80 como tensoativo. As PCHs apresentaram tamanho médio de (303.39 ± 2,01) nm, potencial zeta de +32.50 mV e eficiência de encapsulação de 86.200±1,38%. A liberação do fármaco in vitro foi avaliada em solução salina de tampão fosfato (pH 5,5), usando a mucosa nasal de cabra e o resultado encontrado foi de 82.529% ± 1.308, acima de 28 h. Estudos de cinética de liberação mostraram que a liberação do fármaco das nanopartículas foi por difusão anômala (não fickiana), indicando que é controlada por mais de um processo, ou seja, a superposição dos fenômenos de difusão controlada e intumescimento. As PCHs mostraram resultados de boa estabilidade, encontrada durante os estudos de estabilidade em temperaturas diferentes, como mencionado em diretrizes do ICH. Os resultados revelaram que o sistema de nanopartículas de quitosana contendo cloridrato de selegilina é o mais adequado sistema de liberação de fármacos de ação terapêutica promissora.