Usha Y. Nayak

Glutaraldehyde cross-linked chitosan microspheres for controlled delivery of Zidovudine

Zidovudine-Chitosan microspheres were prepared by a suspension cross-linking method. The chitosan was dissolved in 2% acetic acid solution and this solution was dispersed in the light liquid paraffin. Span-80 was used as an emulsifier and glutaraldehyde as cross-linking agent. The prepared microspheres were slight yellow, free flowing and characterized by drug loading, infrared spectroscopy (IR), differential scanning colorimetry (DSC) and scanning electron microscopy (SEM). The in-vitro release studies are performed in pH 7.4 buffer solution. Microspheres produced are spherical and have smooth surfaces, with sizes ranging between 60–210 µm, as evidenced by SEM and particle size analysis. The drug loaded microspheres showed up to 60% of entrapment and release was extended up to 18–24 h. Among all the systems studied, the 35% Glutaraldehyde crosslinked, microspheres with 1 : 6 drug/chitosan ratio showed 75% release at 12 h. The infrared spectra and DSC thermograms showed stable character of zidovudine in the drug loaded microspheres and revealed the absence of drug–polymer interactions. Data obtained from in vitro release were fitted to various kinetic models and high correlation was obtained in the Higuchi model. The drug release was found to be diffusion controlled.

Development of mucoadhesive buccal films for the treatment of oral sub-mucous fibrosis: a preliminary study

The objective of the present study was to develop the mucoadhesive buccal film of valdecoxib for the treatment of oral sub mucous fibrosis, a localized buccal disease. Valdecoxib, a novel COX-2 inhibitor has been reported to be used in various osteopathic and rheumatoid conditions as oral therapy. The films were made out of chitosan and HPMC K4M as polymers. Sodium taurocholate was used as a permeation enhancer. All the formulations were examined for film thickness, swelling properties, drug content, weight variation, in vitro release studies, bioadhesive force, tensile strength, diffusion studies using pig mucosa and pharmacokinetic study in healthy male volunteers. Prepared films were thin, flexible, smooth and transparent. Bioadhesive force and tensile strength of the optimized formulation were found to be 75 ± 4 kg m−1 S−2 and more than 2.5 kg/3 cm2, respectively. The percent drug content was 98.5 ± 1.3%. The in vitro drug release from the selected formulation showed that about 69.34% of the drug payload was released up to 6 hours. The drug permeation through the dialysis sac and pig buccal mucosa was found to be 62.70% and 54.39%, respectively. Pharmacokinetic studies of the buccal mucoadhesive film showed that the drug was released locally at the target site of action, and a very small amount might have absorbed systemically.

Chronotherapeutic drug delivery for early morning surge in blood pressure: A programmable delivery system

The purpose of the study was to develop pulsatile capsule dosage form of valsartan for controlled delivery. In the majority of individuals blood pressure rises in the early morning hours, which lead to serious cardiovascular complications. Formulations with constant/programmable delivery rates make it possible to deliver drug at definite time or controlled rate in chronopharmacokinetic studies. The prepared system contained swellable polymer (l-hydroxypropyl cellulose (L-HPC), xanthan gum, polyethylene oxide or sodium alginate) together with drug tablet and erodible tablet (L-HPC or guar gum) in a pre-coated capsule. Various formulation factors were investigated through series of tests, in vitro dissolution and ex vivo continuous dissolution-absorption studies. We found that the type, amount of polymers and erodible tablet influenced the drug release. The formulation containing 200 mg sodium alginate and erodible tablet (150 mg) containing 50% guar gum and 46% lactose showed 5-6 h lag time and 10+/-2.1% drug release in initial 6 h following rapid release (99+/-1.7% release in 12 h) of drug was observed. The continuous dissolution-absorption study conducted using everted rat intestinal segment indicated delay in absorption of drug. Thus this approach can provide a useful means for timed release of valsartan and may be helpful for patients with morning surge.

Sonophoresis-mediated permeation and retention of peptide dendrimers across human epidermis

Purpose: The objective of the present study was to assess the effect of sonophoresis on the permeation rate of peptide dendrimers through human skin.

Novel interpenetrated polymer network microbeads of natural polysaccharides for modified release of water soluble drug: in‐vitro and in‐vivo evaluation

Objectives  The objective of this work was to prepare novel interpenetrating polymer network (IPN) microbeads of tamarind seed polysaccharide and sodium alginate for controlled release of the water soluble drug, diltiazem hydrochloride.

Multiparticulate Drug Delivery System of Aceclofenac: Development and In Vitro Studies

The aim of this study was to develop an enteric-coated multiunit dosage form containing aceclofenac, a nonsteroidal anti-inflammatory drug. The pellets were prepared by using extrusion/spheronization method, and the core pellets were coated with a pH-sensitive poly(meth) acrylate copolymer (Eudragit L100-55) to achieve site-specific drug release. The formulated pellets were characterized for percentage yield, size distribution, surface morphology studies, drug content, and flow properties. In vitro dissolution test was used for comparison of drug release profiles of various coated pellets. The practical yield was found to be 90–95%. The particle size of enteric-coated pellets was found to be in the range of 0.59–0.71 mm. The pellets were spherical in shape and surfaces of pellets were found to be rough and showing micropores. Enteric-coated pellets showed good flow properties and in vitro dissolution profile. Dissolution tests were carried out in a USP type II dissolution apparatus in media-simulating pH conditions of the gastrointestinal tract. The release of the aceclofenac from formulated pellets was established to be minimum in the pH 1.2 (<5%) for a period of 2 h, and at pH 6.8, it shows the maximum release (85 ± 5% release within 1 h) which indicates gastric resistance of the formulated pellets. The 20% wt/wt enteric-coated pellets were compared to that of marketed product (tablets), it was observed that pellets showed better release profile. The study concluded that the formulated multiparticulate dosage forms can be used as an ideal drug delivery system for the aceclofenac.

Development and evaluation of sunscreen creams containing morin-encapsulated nanoparticles for enhanced UV radiation protection and antioxidant activity

The objective of present work was to develop novel sunscreen creams containing polymeric nanoparticles (NPs) of morin. Polymeric NPs containing morin were prepared and optimized. The creams containing morin NPs were also prepared and evaluated. Optimized NPs exhibited particle size of 90.6 nm and zeta potential of −31 mV. The entrapment efficiency of morin, within the polymeric NPs, was found to be low (12.27%). Fourier transformed infrared spectroscopy and differential scanning calorimetry studies revealed no interaction between morin and excipients. Transmission electron microscopy and atomic force microscopy revealed that the NPs were spherical in shape with approximately 100 nm diameter. Optimized NPs showed excellent in vitro free radical scavenging activity. Skin permeation and deposition of morin from its NPs was higher than its plain form. Different sunscreen creams (SC1–SC8) were formulated by incorporating morin NPs along with nano zinc oxide and nano titanium dioxide. SC5 and SC8 creams showed excellent sun protection factor values (≈40). In vitro and in vivo skin permeation studies of sunscreen creams containing morin NPs indicated excellent deposition of morin within the skin. Morin NPs and optimized cream formulations (SC5 and SC8) did not exhibit cytotoxicity in Vero and HaCaT cells. Optimized sunscreen creams showed excellent dermal safety. SC5 and SC8 creams demonstrated exceptional in vivo antioxidant effect (estimation of catalase, superoxide dismutase, and glutathione) in UV radiation-exposed rats. The optimized sunscreen creams confirmed outstanding UV radiation protection as well as antioxidant properties.

Controlled release chitosan microspheres of mirtazapine: In vitro and in vivo evaluation

The purpose of the study was to formulate and evaluate controlled release chitosan microspheres of mirtazapine (MTZ) to improve the bioavailability by altering the pharmacokinetic profiles of the drug. Chitosan microspheres were prepared to prolong the release of the drug into the systemic circulation. Microspheres were prepared by a single water in oil (w/o) emulsion technique varying the chitosan/drug ratio, stirring speed and concentration of the crosslinking agent (glutaraldehyde). Drug-polymer compatibility studies were carried out using fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The microspheres were evaluated for encapsulation efficiency, particle size, surface morphology, swelling index, in vitro release, as well as erosion and in vivo studies in rats. The FT-IR and DSC studies revealed no interaction between drug and polymer. The encapsulation efficiency of different formulation varied from 53 ± 1.2% to 78 ± 1.5%. The mean particle size of the optimized formulation F-14 was 106.4 ± 0.5 μm. Surface morphology revealed that chitosan microspheres were discrete and spherical in shape with a porous surface. The release of MTZ from chitosan microspheres was rapid up to 4 h, and then it was continuously and slowly released up to 48 h. Optimized formulation (F-14) was found to be stable under accelerated storage conditions based on International Conference on Harmonisation guidelines. Pharmacokinetic studies revealed that the optimized formulation showed significant increases in systemic exposure (AUC = 177.70 ± 7.39 μg·h/mL), half-life (4.72 ± 0.46 h) and reduced clearance (0.009 ± 0.0001 L/h) compared to pure drug administration. Hence, the present study demonstrates that controlled release formulation of MTZ microspheres using chitosan can improve pharmacokinetic profiles of MTZ.

Development of risperidone liposomes for brain targeting through intranasal route

The present paper is aimed at development of functionalized risperidone liposomes for brain targeting through nasal route for effective therapeutic management of schizophrenia. The risperidone liposomes were prepared by thin film hydration method. Various parameters such as lipid ratio and lipid to drug ratio were optimized by using Design-Expert(®) Software to obtain high entrapment with minimum vesicle size. The surface of the optimized liposomes was modified by coating stearylamine and MPEG-DSPE for enhanced penetration to the brain. The formulations were evaluated for vesicle size, zeta potential, and entrapment efficiency. The morphology was studied by Transmission Electron Microscopy (TEM). In vivo efficacy was assessed by performing pharmacokinetic study in Wistar albino rats following intranasal administration of the formulations in comparison to intravenous bolus administration of pure drug. The mean vesicle size of optimized liposomes ranged from 90 to 100nm with low polydispersity index (<0.5). The entrapment efficiency of optimized liposomes was between 50 and 60%, functionalized liposomes showed maximum entrapment. The TEM images showed predominantly spherical vesicles with smooth bilayered surface. All formulations showed prolonged diffusion controlled drug release. The in vivo results showed that liposomal formulations provided enhanced brain exposure. Among the formulations studied, PEGylated liposomes (LP-16) had shown greater uptake of risperidone into the brain than plasma. High brain targeting efficiency index for LP-16 indicating preferential transport of the drug to brain. The study demonstrated successful formulation of surface modified risperidone liposomes for nasal delivery with brain targeting potential.

Inclusion Complexation of Etodolac with Hydroxypropyl-beta-cyclodextrin and Auxiliary Agents: Formulation Characterization and Molecular Modeling Studies

The present investigation was aimed to prepare inclusion complexes of a therapeutically important nonsteroidal anti-inflammatory drug, etodolac (ETD) with hydroxypropyl-beta-cyclodextrin (HP-β-CD) and to study the effect of l-arginine (l-Arg) as an auxiliary agent on the complexation efficiency of HP-β-CD to improve aqueous solubility and the dissolution property of ETD. The binary and ternary complexes were prepared by physical mixing, coevaporation, and spray drying methods. The complexes were characterized using differential scanning colorimetry (DSC), Fourier transform-infrared spectroscopy (FT-IR), and powder X-ray diffraction (PXRD) studies. The mechanism of inclusion interaction of guest and host was established through 1H NMR, molecular docking, and molecular dynamics studies. On the basis of preliminary screening studies, l-Arg was found to be the most efficient auxiliary agent for the present research problem. The change in crystallinity of ETD was evident from DSC and PXRD studies which indicated the formation of new solid forms. A remarkable increase in apparent stability constant (Kc) and complexation efficiency (CE) of HP-β-CD was observed in the presence of l-Arg in ternary complexes with improvement in solubility and dissolution of ETD than binary complexes. However, inclusion complexes of ETD obtained by computational studies is in good correlation with the results obtained through experimental methods. More stable complex formation with l-Arg was confirmed by molecular simulation studies too. Thus, the present study led to the conclusion that the ternary complex of ETD-HP-β-CD-l-Arg could be an innovative approach to augment the solubility and dissolution behavior of ETD.