Fabrication and in vitro characterization of polymeric nanoparticles for Parkinson's therapy: a novel approach

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.

Formulation and characterization of a novel pH-triggered in-situ gelling ocular system containing Gatifloxacin.

The present research work deals with the formulation and evaluation of in-situ gelling system based on sol-to-gel transition for ophthalmic delivery of an antibacterial agent gatifloxacin, to overcome the problems of poor bioavaila-bility and therapeutic response exhibited by conventional formulations based a sol-to-gel transition in the cul-de-sac upon instillation. Carbopol 940 was used as the gelling agent in combination with HPMC and HPMC K15M which acted as a viscosity enhancing agent. The prepared formulations were evaluated for pH, clarity, drug content, gelling capacity, bioadhesive strength and in-vitro drug release. In-vitro drug release data of optimized formulation (F12) was treated according to Zero, First, Korsmeyer Peppas and Higuchi kinetics to access the mechanism of drug release. The clarity, pH, viscosity and drug content of the developed formulations were found in range 6.0-6.8, 10-570cps, 82-98% respectively. The gel provided sustained drug release over an 8 hour period. The developed formulation can be used as an in-situ gelling vehicle to enhance ocular bioavailability and the reduction in the frequency of instillation thereby resulting in better patient compliance.

Formulation and characterization of a novel pH-triggered in-situ gelling ocular system containing Gatifloxacin.

The present research work deals with the formulation and evaluation of in-situ gelling system based on sol-to-gel transition for ophthalmic delivery of an antibacterial agent gatifloxacin, to overcome the problems of poor bioavaila-bility and therapeutic response exhibited by conventional formulations based a sol-to-gel transition in the cul-de-sac upon instillation. Carbopol 940 was used as the gelling agent in combination with HPMC and HPMC K15M which acted as a viscosity enhancing agent. The prepared formulations were evaluated for pH, clarity, drug content, gelling capacity, bioadhesive strength and in-vitro drug release. In-vitro drug release data of optimized formulation (F12) was treated according to Zero, First, Korsmeyer Peppas and Higuchi kinetics to access the mechanism of drug release. The clarity, pH, viscosity and drug content of the developed formulations were found in range 6.0-6.8, 10-570cps, 82-98% respectively. The gel provided sustained drug release over an 8 hour period. The developed formulation can be used as an in-situ gelling vehicle to enhance ocular bioavailability and the reduction in the frequency of instillation thereby resulting in better patient compliance.

Aceclofenac delivery by microencapsulation using LBL self-assembly for delayed release

Colonic targeting has gained increasing interest over the past years, not just for the transport of drugs for the treatment of local diseases associated with the colon but also for its potential for transporting peptides and proteins, particularly low molecular weight peptide drugs. Without protection, such peptide drugs are usually digested within the gastric and small intestinal sections. In the present work Layer-By-Layer [LBL] self-assembly was utilized to make Aceclofenac single bilayer microcapsules produced by sequential adsorption of positively charged chitosan and negatively charged Pectin on the external surface of negatively charged Aceclofenac microcrystals. Taguchi approach was applied to determine the best concurrence of composition factors that is concentration of chitosan, pectin, centrifugation speed and incubation time. The microcapsules were characterized for encapsulation efficiency, particle size, zeta potential, scanning electron microscopy and in-vitro release kinetics. Surface electric potential of Aceclofenac microcrystals was found to be negative with zeta potential -1.39 mV, in acetate buffer of pH 4. The primary and the secondary deposit layer of chitosan and pectin was found to have a positive and negative charge with zeta potential of +5.57 mV and -22.8 mV respectively. The sequential changing of surface zeta potential after each deposition is a satisfactory indication of the LBL self-assembly of the oppositely charged polyelectrolytes. The average size and encapsulation efficiency of the optimized single bilayer microcapsules [F5] was found to be 20microm and 63.83%, respectively. The ex-vivo percentage cumulative drug release of [F5] in Phosphate buffer pH 6.8 containing 2-4% w/v colonic fecal matter of male albino rat was found to be 98.40%. The optimized batch of microcapsules showed first order release kinetics [R[2]= 0.950] in presence of colonic fecal matter

Development of meloxicam formulations utilizing ternary complexation for solubility enhancement

Meloxicam [an oxicam derivative], a relatively new cyclo-oxygenase inhibitor, is a member of enolic acid group of non-steroidal anti-inflammatory drugs. It is generally used in the treatment of rheumatoid arthritis, osteoarthritis and other joint pains. Meloxicam is practically insoluble in water [8 microg/ml], which directly influences the C[max], T[max], as well as the bioavailability of the drug. In the present study, an attempt has been made to improve the dissolution of Meloxicam by preparation of its solid dispersion using p-cyclodextrin blended with various water soluble polymer carriers i.e., HPMC [methocel IH], methylcellulose [400cps], PVP K30, HPMC [K[4]M], HPMC [50cps]. It is reported that when small amount of water soluble polymer is added to beta-cyclodextrin, its nature of solubilization significantly increases due to increase in the apparent complex stability constant. Phase solubility studies were carried out to evaluate the solubilizing power of beta-cyclodextrin along with various water soluble polymers. The solid dispersion was prepared and formulated into tablets and suspension, which were evaluated on the basis of various official tests. All the studies suggest that formulations of Meloxicam utilizing solid dispersion technique significantly enhances solubility [90 microg/ml] of the drug and results in superior formulations of the drug by using beta-cyclodextrin blended with 0.12% w/w HPMC [Methocel IH]. Ternary complexation is a valuable tool for solubility enhancement of drugs

Formulation and evaluation of mucoadhesive buccal patch of acyclovir utilizing inclusion phenomenon

Mucoadhesive buccal patch releasing drug in the oral cavity at a predetermined rate may present distinct advantages over traditional dosage forms, such as tablets, gels and solutions. A buccal patch for systemic administration of acyclovir in the oral cavity was developed using polymers hydroxy propyl methyl cellulose (K4M), hydroxy propyl methyl cellulose (K15M), sodium carboxy methyl cellulose and poly vinyl pyrolidone (K30), plasticizer poly ethylene glycol (400) and a backing membrane of Eudragit (RL100). The films were evaluated in terms of swelling, residence time, mucoadhesion, release, and organoleptic properties. The optimized films showed lower release as compared to controlled drug delivery systems. Hence, an inclusion complex of acyclovir was prepared with hydrophilic polymer hydroxylpropyl beta-cyclodextrin in the molar ratio of 1:1. The inclusion complex was characterized by optical microscopy, FAB mass spectroscopy, and FTIR spectroscopy. Patches formulated with the acyclovir inclusion complex were evaluated along the same lines as those containing acyclovir alone. The in vitro release data revealed a substantial increase from 64.35 percent to 88.15 percent in the case of PS I and PS II batches, respectively, confirming the successful use of inclusion complexes for the formulation of buccal patch of acyclovir.

Mucoadesivos bucais liberadores de fármacos para a cavidade oral com taxa de liberação pré-determinada podem apresentar distintas vantagens em relação às formas farmacêuticas convencionais como comprimidos, géis e soluções. Neste trabalho, um adesivo bucal para administração sistêmica de aciclovir através da cavidade oral foi desenvolvido empregando-se os polímeros hidroxipropilmetil celulose (K4M), hidroxipropilmetil celulose (K15M), carboximetil celulose sódica e polivinil pirrolidona (K30), polietilenoglicol plastificado (400) e uma membrana suporte de Eudragit (RL100). Os filmes obtidos foram avaliados em termos de intumescimento, tempo de residência, mucoadesão, liberação e propriedades organolépticas. Os filmes otimizados apresentaram liberação mais lenta em comparação a outros sistemas de liberação controlada. Desta maneira, um complexo de inclusão de aciclovir foi preparado com o polímero hidrofílico hidroxipropil beta-ciclodextrina em proporções molares 1:1. O complexo de inclusão foi caracterizado por microscopia ótica, espectrometria de massas FAB e espectroscopia FTIR. Os adesivos formulados com o complexo de inclusão de aciclovir foram avaliados em paralelo com adesivos contendo aciclovir isolado. Os dados de liberação in vitro revelaram um aumento substancial, de 64,34 por cento para 88,15 por cento, nos lotes PS I e PS II, respectivamente, confirmando o sucesso do uso de complexos de inclusão para a formulação de adesivos bucais de aciclovir.