Mukesh R. Patel

Optimizing Oral Controlled Release Drug Delivery Systems usingExperimental Designs

The number of literature reports on the use of design of experiments optimization in development of drug delivery technology has been piling up steadily. This review article provides an updated bird’s eye view survey account on the publications and optimization techniques of different novel controlled release delivery designs for use in oral applications. Such systematic techniques find their use in every type of conventional dosage form and novel drug delivery system. The drug delivery devices investigated for optimization using various designs include oral controlled release tablet. The present manuscript deal with various steps involved in design of experiments optimization methodology using diverse experimental designs. It also deals with a variety of showing literature findings as well as the potential application of such design of experiments procedures on optimization of assorted drug delivery systems. Such an explicit and updated review on drug delivery optimization has not been published anywhere else in the recent past.

Enhanced Solubility and Dissolution Rate of Aceclofenac by Using SprayDrying Techniques

The present study deals with improvement in aqueous solubility of aceclofenac using HPMC K-15M, PVP-K30 and Eudragit RS-100 in varying ratio by spray-drying at optimized condition. The samples of solid dispersion were subjected to fourier transform infra-red spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction morphology (PXRD), scanning electron microscopy (SEM), in vitro drug release and stability studies. A decrease in the melting enthalpy in DSC indicates conversion of crystalline to amorphous state. The results were supported by PXRD, FTIR and SEM data revealed a characteristic decrease in crystallinity. The dissolution studies demonstrated a marked increase in the dissolution rate in comparison with pure drug. The considerable improvement in the dissolution rate of aceclofenac from spray drying, decreased drug crystallinity, altered surface morphology and micronization. The optimized co-crystals exhibited excellent stability on six month storage at accelerated conditions of 40°C and 75% relative humidity. Thus, the solid dispersion obtained by spray drying is a potential tool for improving drug solubility in water.

Development and Evaluation of Bilayer Tablet of Metoclopramide HCl and Aceclofenac

Bilayer tablets are basically used to administer a dosage form with dual release effect or to formulate two incompatible drugs. The main objective of the present research work was to prepare bilayer tablet of Metoclopramide hydrochloride (MTH) and Aceclofenac (ASF) for separate layers to avoid the degradation of the drug, with the desired release pattern and thus to maximize the efficacy of both drugs in combination for the effective treatment of migraine. MTH and ACF were formulated as immediate and conventional release layer respectively. ASF was formulated as conventional release layer using PVP K-30 and MCC as binder and disintegrants respectively. MTH was formulated as immediate release layer by using various disintegrants like Sodium starch glycolate (SSG), Cross carmellose sodium (CCS) and Pre-gelatinized starch (PGS). Mixture design technique was used to find out the optimized quantity of the super disintegrants. Disintegration time (DT) and drug release at 15 min (Rel15min) were taken as dependent variables while quantity of super disintegrants was taken as independent variable. SSG and CCS in a concentration of 7.5% and 4.5% respectively gave a DT of 9 sec, and 98.67% release at 15 min (Rel15min). Stability studies of bilayer tablets as well as physical mixture were carried out and the samples were evaluated with DSC, FT-IR and % content of drug. Bi-layer tablet was suitable for preventing direct contact of these two drugs and thus to maximize the efficacy of combination of two drugs for migraine.

Recent Patents Survey on Self Emulsifying Drug Delivery System

Self-Emulsifying Drug Delivery System is a unique feasible approach to overcome low oral bioavailability problem which is associated with the hydrophobic drugs due to their unparalleled potential as a drug delivery with the broad range of application. The estimated 40% of active pharmaceuticals are poorly water soluble. Now recently, formulation containing oral SEDDS has received much interest as it solve problems related to oral bioavailability, intra and inter-subject variability and lack of dose proportionality of hydrophobic drugs. Now a days, it is the first way to investigate the development of any kind of innovative dosage forms. Many important in-vitro characteristics such as surfactant concentration, oil/surfactant ratio, emulsion polarity, droplet size and zeta potential play an important role in oral absorption of drug from SEEDS. It can be orally administered in the form of SGC or HGC and also enhances bioavailability of drugs to increase solubility and minimizes the gastric irritation. After administration the drug remains entrapped in the oily droplets (inside the droplet or in the surfactant`s film at the interface) of the emulsion that are formed in the GIT upon self-emulsification process. It is also a bit problematic to say that the drug is being released from SMEDDS, it would be more precise to say that it diffuses out of oily droplets into the GIT media resulting in the formation of an equilibrium between the drug dissolved in oily droplets and the outer dispersed media (e.g. GIT fluids). Many of the application and preparation methods of SEDDS are reported by research articles and patents in different countries. We present an exhaustive and updated account of numerous literature reports and more than 150 patents published on SEDDS in the recent period. This current patent review is useful in knowledge of SEDDS for its preparations and patents in different countries with emphasis on their formulation, characterization and systematic optimization strategies, thus paving the way for accelerated progress into the SEDDS application in pharmaceutical research as well as patents on SEDDS methods.

Formulation and evaluation of orodispersible film of levocetrizine dihydrochloride

The main objective of this study was to develop sol id self-nanoemulsifying drug delivery system (S-SNE DDS) of Irbesartan (IRB) for enhancement of its solubility and dissolution rate. In this study, a novel liquid SNEDDS containing Irbesartan was formulated and further de veloped into a solid form by spray drying technique using Aerosil 200 as solid carrier. The solubility of IRB was determined in various oils, surfactants and co -surfactants to select the best candidates for IRB for further stud y. Pseudoternary phase diagrams were constructed to i entify the efficient area of self-nanoemulsification. Based on preliminary screening of different unloaded SNEDDS formulae, eight formulae of IRB loaded SNEEDS were prepared u sing Capryol 90, Cremophor RH40 and Transcutol HP a s oil, surfactant and cosurfactant respectively. The optimized IRB loaded SNEDDS formulae were evaluated for effect of dilution (with different volumes at different pH values), efficiency of self-emulsification, viscos ity, optical clarity, morphological characterization, drug loading effici ency, in-vitro drug release, droplet size analysis as well as polydispersity index (PDI). SNEDDS formulae were al so tested for thermodynamic stability and zeta pote ntial to confirm the stability of the prepared SNEDDS. Resul ts showed that the mean droplet size of all reconst ituted SNEDDS was found to be in the nanometric range with optimum PDI values. All formulae also showed rapid emulsification time, good optical clarity, and high drug content; and found to be highly stable. Trans mis ion electron microscopic images showed the formation of spherical and homogeneous droplets with a size sma ller than 50nm, which satisfies the criteria of nanometric si ze range required for nanoemulsifying formulae. Invitro release of IRB from SNEDDS formulae showed that more than 9 9% of IRB release in approximately 90 minutes. Opti mized SNEDDS formulae with the smallest particle size, ra pid emulsification time, best optical clarity, and maximum drug content and rapid in-vitro release were selected to be developed into solid self-nanoemulsifying drug delivery system (S-SNEDDS) using spray drying technique. The prepar ed S-SNEDDS formulae were evaluated for flow proper ties, differential scanning calorimetry (DSC), scanning e lectron microscopy (SEM), reconstitution properties , drug content and in-vitro dissolution study. It was foun d that S-SNEDDS formulae showed good flow properties and hig h drug content. Reconstitution properties of S-SNEDDS showed spontaneous self-nanoemulsification and no sign of phase separation. DSC thermograms revealed that IRB was in solubilized form and FTIR supported these f indings. SEM photographs showed smooth uniform surface of SSNEDDS with less aggregation. Results of the in-vit ro drug release showed that there was great enhancement in dissolution rate of IRB.

Recent Survey on Nanosuspension: A Patent Overview

The major goals of designing nanosuspension of nanosize materials are increasing due to their tremendous potential as a drug delivery system with the wide range of applications. Nanosuspension is a unique tool for improving the bioavailability of poorly soluble drugs. Nanosuspension drug delivery has wide range of application like oral, injectable, transdermal, inhalation, peroral, ocular, pulmonary and topical etc. by improviing the bioavailability, reducing the dose, gastric irritation, decreasing intra subject variability and increasing adhesivness with intestinal membrane. Recently, nanosuspension has been received much interest as a way to resolve solubility and stability problem because of their cost-effectiveness and technical simplicity compare to other liposome and colloidal drug carriers. Nanosuspensions are engaged to control particle size, surface properties and release of pharmacologically active agents in order to achieve the site-specific action of the drug at the therapeutically optimal rate, improve the bioavaibility of drug with poor solubility and dose regimen. Application and preparation method of nanosuspension has been reported by research articles and patented in different countries. Most of the marketed nanosuspensions are in preclinical and clinical based study for its application. More than 100 patents have been published on nanosuspensions by the recent days. This patent reviews covers different methods of pharmaceutical preparation and applications in drug delivery as well as the recent marketed published or granted patent surveys. This patent review is useful in enhance the knowledge of controlled drug delivery and applications.

Strategies to design porosity osmotic tablet (POT) for delivering low and pH-dependent soluble drug using an Artificial Neural Network (ANN)

This article characterizes the activities required to launch a new pharmaceutical molecule into the market, summarizes studies that have attempted to pinpoint the research and development costs incurred per approved new molecule, and analyzes the various critiques levied against published R&D cost estimates. It finds that by any reckoning, R&D costs per approved molecule have risen sharply over time, most likely at a rate of approximately 7 percent per year after stripping out the effects of general economic inflation.A is a newer NSAID, used in treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. Aceclofenac has shorter biological half-life around 4 h which makes it suitable for modified release to improve bioavailability and to reduce dosing frequency. Present work was aimed to develop and evaluate aceclofenac modified release (Triple Layer Tablet) TLT following direct compression technique using natural and synthetic polymers. Aceclofenac TLT containing immediate-releaselayer (IM) as first layer, controlled-release-layer (CR) as second layer and ethyl cellulose layer as barrier-layer (BL) were prepared. IM was optimized by D-optimal design where 16 formulations (IM1 – IM16) were developed by using super disintegrating agents like mannitol and SSG. CR was optimized by 32 full factorial design and 9 batches (CN1–CN9 & CS1–CS9) were developed using natural and synthetic polymers like guar gum, xanthan gum and HPMC K100 CR, HPMC K100 LVCR respectively. Drugpolymers compatibility was evaluated by Infrared spectroscopy, where all compositions were found compatible without any interaction. All formulations were evaluated for various post-compression parameters like disintegration time (DT), swelling index, hardness, friability and weight variation etc., and results were found in desirable range. IM and CR formulations were evaluated for drug release behavior in pH 6.8 phosphate buffer and best release compositions among batches were chosen to prepare TLT with BL to modify the release. Among IM formulations least DT was found in IF9 with 90.86% drug release in 10 min 21 sec so, IF9 was claimed as best composition. Among CR formulations the best compositions found were CN3 and CS6 with Time at 47.38 % and 26.42% drug release around 8 h respectively and, were then developed as triple layered tablets with IF9 where drug release was extended up to 24 h.H compounds have received considerable attention owing to their variety of biological activities, especially as inhibitors of PDE5 extracted from human platelets, HIV-1 reverse transcriptase, human EPK2, cyclin-dependent kinas. Also, heterocyclic nitrogen compounds are indispensable structural units for medicinal chemists and used as antibiotics, anthelmintics, antiviral, antidepressant, and anti-inflammatory. In view of these observations we evaluate some new poly hetero cyclic compounds which were previously synthesized according to for their analgesic, anti-inflammatory and anti-microbial activities in comparison to some reference drugs. Pyrimidines present an interesting group of compounds many of which possess wide-spread pharmacological properties such as antidepressant, antimicrobial, anticancer, and anticonvulsant activitiesM drugs combination is a promising strategy in biomedical fields, such as cancer chemotherapy, tissue engineering. The multi-drug system enables to be delivered with multiply targets and exhibits the additive or synergistic effects of drugs. However, the specific distinct drug release kinetics of the multiply drugs are required to meet the clinical needs, especially in the combined therapy of tissue regeneration and tumor chemotherapy. In order to deliver the individual drug at optimal dosages, the release behaviors of each drug in multi-drug systems should be controlled independently. Therefore, two kinds of nanoparicles with core-shell structure (PVP/PLGA and PCL/PLGA) were fabricated by coaxial electrospray in this paper. Each kind of nanoparticles can both encapsulate the hydrophilic rhodamine B and hydrophobic naproxen in one single step efficiently. The monodisperse size distribution as well as the desired core-shell structure was observed. These two multi-drug systems with dual drug loaded exhibited different distinct release profiles, attributing to the distinct core-shell structures of nanoparticles and the difference of two drugs in hydrophilic properties. Meanwhile, the release profiles of encapsulated drugs with different amount were investigated as well. The drug release behaviors were dominated by the following processes: water penetration, surface drug release, outer drug diffusion with shell polymer erosion, inner drug diffusion and nanoparticle collapse. The results suggested that the distinct release kinetics of multiply drugs fabricated by coaxial electrospray can be obtained and tuned to fulfill the clinical requirement in combination therapy.Aspirin suppositories are in commercial use, suffer with side effects such as irritation, burning sensation, rectal hemorrhage. The aim of the present work is to formulate aspirin nanoparticles loaded suppositories and to perform In vitro investigation for the prepared suppositories. Initially aspirin-chitosan nanoparticles were prepared by ionic gelation method and the nanoparticles evaluated for different In vitro evaluation studies; based on results the best formulation was selected and in order to know the diffusion efficiency, different compositions of aspirin glycerogelatin suppositories were prepared and subjected to various In vitro evaluation studies and best composition was selected. From the previously performed evaluation studies best formulation from aspirin nanoparticles incorporated in to selected glycerol gelatin bases and evaluated for In vitro characteristics. The results indicates that formulation Fa9 Aspirin nanoparticles were proved to be best formulation with 88.3±1.1 % of drug release at the end of 24hr, with zero drug release. In vitro characterization performed for aspirin suppositories indicates that Fs2, Fs4, Fs9 and Fa11 was proved to be best composition with highest percentage of drug release at the end of 60 minutes with 98.06±1, 99.3±0.45, 97.6±1.8 and 97±1 drug release and other characteristic studies performed indicates that all formulation are ideal characteristics. Previously selected bases composition used for the loading of nanoparticles based on displacement value results indicates that drug release appears with a lag phase initially and controlled for a period of 24hr.Orally dissolving tablets (ODT) provides a patient compliance solution for patients swallowing difficulties. Foam granulation is a newer technique that promises better distribution of the granulating system and better properties of the produced tablets. Aceclofenac (anti-inflammatory and analgesic) was selected as the model drug. The poor hydrophilicity of the drug results in variable dissolution rate and poor bioavailability. In this study, we tried to prepare aceclofenac ODT using the newer technique and various types of disintegrants, glidants, and lubricants. The resulted tablets were evaluated for hardness, friability, weight variation, in vitro disintegration time, and wetting time. All the formulation showed acceptable disintegration time. It was concluded that the prepared aceclofenac ODT by foam granulation technique using selective range of excipients can provide a dosage form with better patient compliance and effective therapy.