Sunil Kumar Prajapati

Performance evaluation of PAMAM dendrimer based simvastatin formulations

The purpose of this investigation was to evaluate the performance of poly (amidoamine) (PAMAM) dendrimers, with three different surface groups, to be used as drug carriers. Drug-dendrimers complexes were investigated for solubility studies, dissolution studies, in vitro drug release studies, and for stability studies. The solubility enhancement was found maximum with PEGylated dendrimers (33 times) followed by amine (23 times) and hydroxyl (17.5 times) dendrimers. The solubility profile of simvastatin-dendrimer complex showed a linear correlation (Higuchi A(L)-type diagram) between solubility and dendrimers concentration. The formation of the complexes between drug molecules and dendrimers were characterized by the FTIR spectra of these complexes, showing the appearance of the bond formed between the functional groups of the drug (OH and COOH) and dendrimers (NH(2) and OH). The drug-dendrimer complexes displayed the controlled release action during in vitro release studies. Pure simvastatin (SMV) was released in 5h whereas the PEGylated dendrimers-SMV complexes released the drug up to 5 days. The non-PEGylated formulations released the drug up to 24h. Formulations with amine and PEGylated dendrimers were subjected to accelerated stability studies. Formulations with amine dendrimers were found to be most stable in dark, low temperature (0°C) whereas the dark, RT was most suitable storage conditions for formulation with PEGylated dendrimers.

Pharmacokinetic and Pharmacodynamic Studies of Poly(amidoamine) Dendrimer Based Simvastatin Oral Formulations for the Treatment of Hypercholesterolemia

The aim of this investigation was to evaluate the in vivo potential of poly(amidoamine) dendrimers (PAMAM) based simvastatin (SMV) formulations as nanoscale drug delivery units for controlled release action of simvastatin. Drug-dendrimer complexes were prepared and characterized by Fourier transform infrared (FTIR) spectroscopy. In a pharmacodynamic study, the percent increase in cholesterol was less with PAMAM dendrimer formulations as compared to pure drug. The cholesterol level was increased to 20.92% with pure SMV, whereas it was 11.66% with amine dendrimer, 11.49% with PEGylated dendrimer, and 10.86% with hydroxyl dendrimer formulations. Reduction in the increase in triglyceride and low density lipoprotein level was also more prominent with the drug-dendrimer formulations. The order of increase in high density lipoprotein level was PEGylated PAMAM-SMV (4.04%) > PAMAM-amine-SMV (2.57%) > PAMAM-hydroxyl-SMV (1.48%) > pure SMV (1.09%). Dendrimer-SMV formulations showed better pharmacokinetic performances than pure SMV suspension. The peak plasma SMV concentration increased from 2.3 μg/mL with pure SMV to 3.8 μg/mL with dendrimer formulations. The dendrimer mediated formulation had 3-5 times more mean SMV residence time than pure SMV. Furthermore, SMV absorption and elimination rates were decreased significantly, showing controlled release of SMV from the dendrimer formulations.

Moxifloxacin loaded gelatin nanoparticles for ocular delivery: Formulation and in-vitro, in-vivo evaluation.

The current research focuses on developing positively charged gelatin nanoparticles loaded with moxifloxacin for its effective ocular delivery and controlled release in corneal eye layer. We selected type A gelatin because of its biodegradable and non-toxic nature as the polymer of choice for fabricating the nanoparticles by a modified two step desolvation technique. The produced nanoparticles were positively charged (+24±0.12mV) with a narrow particle size of 175±1.11nm as measured by dynamic light scattering (DLS). The in-vitro drug release from the nanoformulations exhibited a burst effect in the first hour followed by a controlled release of the drug for the subsequent 12h. The Korsmeyer-Peppas model showed better linearity and the formulations displayed non-Fickian drug release pattern. The optimized formulation was assessed for its utility as an anti-bacterial agent and its effectiveness was tested on the corneal eye surface of rabbits. The in-vivo tolerance tests revealed that the drug loaded nano-formulations was non-irritant to the ocular tissues indicating its safety. The in-vivo anti-bacterial activity of the nanosuspension was more effective against S. aureus than the commercially market product, MoxiGram®. Microbiological efficacy assessed against B. subtilus using cup-plate method suggested that our fabricated nanosuspension possess better anti-microbial activity as compared to the commercial agent, MoxiGram® revealing promising potentials for the currently developed gelatin based nanoformualtions.

Nanosponges: a potential nanocarrier for novel drug delivery-a review

Abstract The ideal delivery system will solubilize the drug, lead the therapy to the target site, and release the therapy to fulfill the individual need of the patient and disease stage. Nanosponges are one of such effective drug carriers which conquer the problems of drug toxicity and poor bioavailability as they can load both hydrophilic and hydrophobic drugs. Nanosponges are tiny in size with a 3-dimensional network and a nanometric cavity size. Nanosponges are highly porous having unique ability to entrap active moieties and offer a unique advantage of programmable release. They are biologically safe and simple to produce. Nanosponges can be prepared by cross linking different types of cyclodextrins with a carbonyl or a dicarboxylate compound as a cross linker. Nanosponge technology has been explored for various applications like enhancing the bioavailability of drug molecules and delivery of drugs into the oral, topical as well as parenteral routes. Nanosponges can also be used as a carrier for biocatalysts in the delivery and release of enzymes, proteins, vaccines and antibodies.

Formulation and evaluation of novel stomach specific floating microspheres bearing famotidine for treatment of gastric ulcer and their radiographic study

ABSTRACT Objective To develop and characterize multiple-unit-type oral floating microsphere of famotidine to prolong gastric residence time and to target stomach ulcer. Methods The floating microspheres were prepared by modified solvent evaporation method. Eudragit S-100 was used as polymer. Microspheres were characterized for the micromeritic properties, floating behavior, entrapment efficiency and scanning electron microscopy. The in-vitro release studies and floating behavior were studied in simulated gastric fluid at pH 1.2. Different drug release kinetics models were also applied for all the batches. Selected formulations were also subjected for X-ray radiographic study. Results Floating microspheres were successfully prepared by modified solvent evaporation technique. Microspheres showed passable flow properties. The maximum yield of microspheres was up to (95.11±0.35)%. On the basis of optical microscopy particle size range was found to be ranging from (52.18±182.00) to (91.64±5.16) μm. Scanning electron microscopy showed their spherical size, perforated smooth surface and a cavity inside microspheres. Microspheres were capable to float up to 20 h in simulated gastric fluid. X-ray radiographic studies also proved its better retention in the stomach. Conclusions On the basis of the results, such dosage forms may be a good candidate for stomach targeting and may be dispensed in hard gelatin capsules.

Synthetic Methods, Chemistry, and the Anticonvulsant Activity of Thiadiazoles

The chemistry of heterocyclic compounds has been an interesting field of study for a long time. Heterocyclic nucleus 1,3,4-thiadiazole constitutes an important class of compounds for new drug development. The synthesis of novel thiadiazole derivatives and investigation of their chemical and biological behavior have gained more importance in recent decades. The search for antiepileptic compounds with more selective activity and lower toxicity continues to be an active area of intensive investigation in medicinal chemistry. During the recent years, there has been intense investigation of different classes of thiadiazole compounds, many of which possess extensive pharmacological activities, namely, antimicrobial activity, anticonvulsant, antifungal antidiabetic, anti-inflammatory, antioxidant, and antituberculosis activities, and so forth. The resistance towards available drugs is rapidly becoming a major worldwide problem. The need to design new compounds to deal with this resistance has become one of the most important areas of research today. Thiadiazole is a versatile moiety that exhibits a wide variety of biological activities. Thiadiazole moiety acts as “hydrogen binding domain” and “two-electron donor system.” It also acts as a constrained pharmacophore. On the basis of the reported literature, we study here thiadiazole compounds and their synthetic methods chemistry and anticonvulsant activity.

Design and Evaluation of Ocusert for Controlled Delivery of Flurbiprofen Sodium

Purpose: The basic objective of this study is to develop the Flurbiprofen sodium soluble ocusert to increase patient compliance by improving local delivery of the drug. Materials and Methods: Three different polymers were used in combination to prepare the rate controlling membrane. The drug reservoir was prepared by using hydroxy propyl methyl cellulose. Ocuserts were evaluated for their physicochemical parameters. The optimized formulations were further evaluated for accelerated stability studies, eye irritancy tests, and for in vivo drug release studies. Results: Ocuserts were found stable at room temperature and showed a strong positive correlation between in vitro and in vivo drug release. Conclusion: An appropriate combination of hydrophilic and hydrophobic polymers provides better control of drug delivery.