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

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.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

PLACKETT-BURMAN DESIGN AS A TOOL FOR SCREENING AND PROCESS OPTIMIZATION OF RIVASTIGMINE-LOADED LIPID NANOCARRIERS

Objective: Plackett–Burman experimental design is used to identify the most important factors early in the experimentation phase when complete knowledge about the system is usually unavailable. The objective of this study was to screen out the most important factors affecting the size and entrapment efficiency of rivastigmine hydrogen tartrate (RHT) nanostructured lipid carriers (NLCs). Methods: The RHT-loaded NLC was prepared by the modified solvent emulsification-diffusion method. The independent variables selected for Plackett–Burman design were drug: lipid ratio, solid lipid/liquid lipid (S/L) ratio, concentration Ryoto sugar ester (%w/v), the concentration of poloxamer 188 (%w/v), sonication time (min), sonication amplitude, and stirring time (h). Results: The R2 value for the particle size equation was 86.16%. p value was (<0.05) 0.048 in case of sonication time. In case of entrapment efficiency, the R2 value was 87.12%. The p value (p<0.05) for S/L ratio and the Ryoto sugar (% w/v) was 0.028 and 0.042, respectively. Conclusion: It can be concluded that sonication time has a significant effect on particle size, whereas S/L ratio and Ryoto sugar ester concentration have a significant effect on entrapment efficiency

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% to 88.15% 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% para 88,15%, 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

Antihepatotoxic Potential of Citrullus colocynthis Root Extract, Fractions and Isolated Compounds

Medicinal plants are considered to be effective and safe alternative treatment for liver toxicity. The article reveals the hepatoprotective activity of the ethanolic extract of the roots of the Citrullus colocynthis commonly known as INDRYAN using carbon tetrachloride (CCl4) experimental model in albino rats. After receiving significant protection of Ethanolic extract on liver the extract further undergone fractionation into three fractions & the activity was localized in the toluene fraction. These on purification led to the isolation of two pure compounds which were identified as - Cucurbitacin B[1] and Colocynthin [2]. The pure compound shows reduction in enzymatic level viz. (SGOT 68.09%, SGPT 63.64%, ALP 76.81%, BL 68.22%) and (SGOT 71.28%, SGPT 65.24%, ALP 80.68%, BL 54.92%) at 50 mg/ kg dose respectively whereas drug Silymarin showed reduction as (SGOT 79.73%, SGPT 74.26%, ALP 87.88%,BL 82.75% ) at 25 mg/kg dose level. On comparing the obtained data it was observed that the roots of C. colocynthis Sch. exhibited significantly better hepatoprotective activity, thus justifying the traditional claims

QUANTIFICATION USING ULTRAVIOLET SPECTROSCOPY METHOD AND IN VITRO STABILITY STUDY OF NANOVESICULAR SYSTEM CONTAINING PHYTIC ACID

Objective: The quantification of drug and stability of nanoparticulate delivery systems is one of the major apprehensions in biomedical applications. The present research work was attempted to quantify phytic acid by utilizing ultraviolet (UV) spectroscopy method and to evaluate the stability of nanovesicular (niosomes) system containing phytic acid.Methods: Niosomes containing phytic acid were developed by thin-film hydration method. Nanoformulation was subjected to stability testing as per the International Council for Harmonisation (ICH) guidelines. The formulation was stored at 30°C±2°C and 65%±5% RH, samples were withdrawn at 15th, 30th, 60th, 90th, 120th, and 180th day of analysis and examined for the integrity of vesicular/particle size, polydispersity index, zeta potential, and percent encapsulation efficiency.Results: Prepared nanoformulation displayed a straight line (y=mx+c) equation of y=−0.0309x+1.0413. Optimized batch of niosomes, which was prepared including dicetylphosphate showed zeta potential value of −36±0.36. Stability study showed that prepared niosomal formulation was stable up to 180 days at room temperature.Conclusion: Findings of the current research work suggested that UV spectroscopy method can be effectively used for the quantification of phytic acid and niosomal formulation of phytic acid. The formulation was found to be stable as per the ICH guidelines for stability testing

FORMULATION AND EVALUATION OF FLOATING-MUCOADHESIVE MICROSPHERES OF NOVEL NATURAL POLYSACCHARIDE FOR SITE SPECIFIC DELIVERY OF RANITIDINE HYDROCHLORIDE

Objective: Localization of ranitidine hydrochloride (RH) into the upper part of the intestinal tract is beneficial for better drug bioavailability. Present work described the method of preparation of novel plant polysaccharide based floating microspheres for delivery of the drug into the stomach. Methods: Polysaccharide was extracted from the seeds of plant Tamarindus indica (TI). Extracted polysaccharide was evaluated for some physicochemical parameters. Floating-mucoadhesive microspheres were prepared by using extracted polysaccharide as mucoadhesive excipients while eudragit as a release controlling polymers by using emulsion crosslinking method. Chemical crosslinking was done by using epichlorohydrin. Prepared microspheres were evaluated for their drug-polymer compatibility study by using fourier transform infrared spectroscopy (FT-IR). Further characterization such as size, surface properties, swelling index, percentage encapsulation, in vitro buoyancy and drug release was performed. Results: FT-IR study confirms the chemical crosslinking of extracted polysaccharide and also drug stability during processing of microspheres. The size of microspheres was in the range of 5.38 to 7.84 µm. SEM images revealed that all batches were of spherical in size and smooth surface. The swelling index showed better swelling in the range of 158-257 percentages. Encapsulation efficiency was found to be decreased by decreasing the concentration of polysaccharide. In vitro buoyancy study possesses that formulation F1 showed better floating ability as compared to the others. Finally, in vitro drug release study revealed that prepared microspheres were able to release the 100% drug within 8-12 h, indicating sustain release behavior. Conclusion: Present study concludes that polysaccharide of TI may be used as excipients for the preparation of floating-mucoadhesive microspheres

Fotokemijska toksičnost lijekova namijenjenih okularnoj uporabi

The present investigation was undertaken to evaluate the possible ocular phototoxicity of drugs used in ophthalmic formulations. Sulphacetamide, ketoconazole, voriconazole, diclofenac, and ketorolac were assessed in the concentrations available in the market for their ocular use. The suitable models viz Hen’s Egg Test Chorioallantoic Membrane (HET-CAM) test, Isolated Chicken Eye (ICE) test, and Red Blood Cell (RBC) haemolysis test as recommended by ECVAM, ICCVAM, and OECD guidelines were performed. Results of HET-CAM and ICE tests suggest that sulphacetamide is moderately toxic in the presence of light/UV-A and very slightly irritant without irradiation. Ketoconazole and voriconazole were found slightly irritant in presence of light/UV-A and non-irritant in dark. Diclofenac and ketorolac demonstrated slight irritancy in the light and were found to be non-irritant in dark. The results suggest that some of the drugs have potential toxic effect in the presence of light. The extent of phototoxicity might get extended when used for longer time. The recommendation is that these drugs should be stored and used in the dark for a specified time and be labelled with specific instructions for patients, especially for those working longer in the sunlight.Cilj ovog ispitivanja bio je istražiti moguću okularnu fototoksičnost lijekova koji se koriste u oftalmološkim formulacijama. Sulfacetamid, ketokonazol, vorikonazol, diklofenak i ketorolak ispitivani su u koncentracijama koje su dostupne na tržištu u njihovom obliku koji je namijenjen za okularnu uporabu. Primijenjeni su testovi iritacije na kokošjem jajetu (Hen’s Egg Test Chorioallantoic Membrane - HETCAM), izoliranom kokošjem oku (Isolated Chicken Eye - ICE) i test hemolize crvenih krvnih stanica (Red Blood Cell - RBC) prema preporukama ECVAM-a, ICCVAM-a i OECD-a. Rezultati HET-CAM i ICE testova upućuju na umjerenu toksičnost sulfacetamida u prisutnosti svjetla/UV-A te vrlo blagu iritaciju u mraku. Ketokonazol i vorikonazol pokazali su blagu iritaciju u prisutnosti svjetla/UV-A te nikakvu iritaciju u mraku. Diklofenak i ketorolak pokazali su blagu iritaciju na svjetlu i nikakvu iritaciju u mraku. Rezultati upućuju na moguću toksičnost nekih od navedenih lijekova u prisutnosti svjetla. Razmjer fototoksičnosti može biti povećan pri produljenoj uporabi lijeka. Preporučuje se čuvati navedene lijekove na zatamnjenome mjestu te ih označiti odgovarajućim uputama za korištenje, osobito za osobe koje su dulje vrijeme izložene sunčevoj svjetlosti

Tea tree and jojoba oils enriched bigel loaded with isotretinoin for effective management of acne

The study is aimed at the preparation of isotretinoin (ITR) loaded bigel for acne therapy. Bigels were enriched with tea tree and jojoba oils known to bestowed soothing properties. Bigels were evaluated for the physiochemical parameters viz. pH, viscosity, etc, in vitro release, and ex vivo permeation. The results displayed enhanced retention and antimicrobial potential of optimized B2 gel when compared with plain gel and other formulations. Thus the bigel of isotretinoin could be a promising delivery system for the treatment of acne

Tea tree and jojoba oils enriched bigel loaded with isotretinoin for effective management of acne

158-163The study is aimed at the preparation of isotretinoin (ITR) loaded bigel for acne therapy. Bigels were enriched with tea tree and jojoba oils known to bestowed soothing properties. Bigels were evaluated for the physiochemical parameters viz. pH, viscosity, etc, in vitro release, and ex vivo permeation. The results displayed enhanced retention and antimicrobial potential of optimized B2 gel when compared with plain gel and other formulations. Thus the bigel of isotretinoin could be a promising delivery system for the treatment of acne

An updated review on Physalis peruviana fruit: Cultivational, nutraceutical and pharmaceutical aspects

97-110Plants have always been rich sources of medicinally active constituents in the quest for curing numerous diseases. Among those, Physalis peruviana has been utilized traditionally as a therapeutic (antispasmodic, diuretic, antiseptic, sedative, and analgesic) and nutraceutical herb. It contains numerous active components like essential minerals, α-linolenic acid, iron, vitamins, carbohydrates, phytosterols etc. Its potential as a multifunctional agent in beverages, foods and nutraceutical industries makes it an important crop for consideration. From the agricultural point of view, this fruit is a profitable commercial crop for arid regions also and does not require much effort and investment for cultivation. It easily grows in wild and arid regions. Despite being a nutraceutical and a medicinally important crop, its utilization is not up to the mark. Thus the objective of the present review was to explore and emphasize the nutraceutical and therapeutic potential of Physalis peruviana. It provides exhaustive insight into the origin, distribution, cultivation, harvesting, active constituents and its prospective utility in food, nutrition and pharmaceutical industries