Monica Gulati

Aquasomes: a promising carrier for peptides and protein delivery

UNLABELLED Aquasomes are one of the most recently developed delivery systems that are finding a niche as peptide and protein carriers. These are nanoparticulate carrier systems with three-layered self-assembled structures. They comprise a central solid nanocrystalline core coated with polyhydroxy oligomers onto which biochemically active molecules are adsorbed. The solid core provides the structural stability, while the carbohydrate coating protects against dehydration and stabilizes the biochemically active molecules. This property of maintaining the conformational integrity of bioactive molecules has led to the proposal that aquasomes have potential as a carrier system for delivery of peptide-based pharmaceuticals. The delivery system has been successfully utilized for the delivery of insulin, hemoglobin, and various antigens. Oral delivery of enzymes like serratiopeptidase has also been achieved. This article discusses the problems faced in the delivery of clinically important peptides and presents aquasomes as a reliable approach to troubleshoot them. FROM THE CLINICAL EDITOR Aquasomes are nanoparticulate carrier systems with three layered self-assembled structures enabling the delivery peptide/protein based pharmaceuticals including enzymes, structural proteins or even antigens. This article discusses the problems faced in the delivery of clinically important peptides and presents aquasomes as a reliable approach to troubleshoot them.

Application of Liposomes in Treatment of Rheumatoid Arthritis: Quo Vadis

The most common treatments for rheumatoid arthritis include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease modifying antirheumatic drugs (DMARDs), and some biological agents. However, none of the treatments available is able to achieve the ultimate goal of treatment, that is, drug-free remission. This limitation has shifted the focus of treatment to delivery strategies with an ability to deliver the drugs into the synovial cavity in the proper dosage while mitigating side effects to other tissues. A number of approaches like microemulsions, microspheres, liposomes, microballoons, cocrystals, nanoemulsions, dendrimers, microsponges, and so forth, have been used for intrasynovial delivery of these drugs. Amongst these, liposomes have proven to be very effective for retaining the drug in the synovial cavity by virtue of their size and chemical composition. The fast clearance of intra-synovially administered drugs can be overcome by use of liposomes leading to increased uptake of drugs by the target synovial cells, which in turn reduces the exposure of nontarget sites and eliminates most of the undesirable effects associated with therapy. This review focuses on the use of liposomes in treatment of rheumatoid arthritis and summarizes data relating to the liposome formulations of various drugs. It also discusses emerging trends of this promising technology.

Brain Permeable Nanoparticles

The brain is one of the least accessible organs of the body, thus making the delivery of neurotherapeutics almost a challenge. Despite its relatively high nutrient support and exchange requirements, the uptake of any compound is strictly regulated by the blood brain barrier (BBB). As a consequence, BBB prevents effective treatment of many severe and life threatening diseases like brain cancer, epilepsy, Alzheimers disease, schizophrenia etc. Numerous drug delivery strategies have been developed to circumvent this barrier. One such approach is the use of nanoparticles. Nanoparticles form solid, colloidal drug delivery system that consists of macromolecular materials in which the active principle is dissolved, entrapped or encapsulated or onto which the active principle is adsorbed or attached. Brain targeted polymeric nanoparticles have been found to increase the therapeutic efficacy and reduce the toxicity for a large number of drugs. By coating the nanoparticles with surfactants, higher concentrations of drugs can be delivered to the brain. The article presents various approaches used in design and delivery of nanoparticles to brain. It also reviews various patents that describe the use of nanoparticles to deliver various neurotherapeutics and neurodiagnostics to brain.

Facts, fallacies and future of dissolution testing of polysaccharide based colon-specific drug delivery

Colonic diseases like ulcerative colitis, Crohns disease, and colon cancer are on rise due to variations in the dietary and lifestyle habits. Increase in prevalence of such diseases has augmented the interest of researchers in colon targeted drug delivery systems. Polysaccharide coating has emerged as one of the most successful approaches in this direction. Evaluation of such systems, however, demands an efficient dissolution method in terms of convenience, economy, relevance and reproducibility. It is problematic to mimic the dynamic and ecologically diverse features of the colon. A number of dissolution approaches were tried which include incorporation of polysaccharide-degrading enzymes, rat caecal contents, human faecal slurries, and multi-stage culture systems. Till date, pursuit for cost-effective and animal-sparing colon-specific bio-relevant dissolution media has been a foremost challenge facing pharmaceutical scientists over many decades. This article reviews various dissolution methods adopted to mimic the in vivo performance of dosage forms that are used for colon targeting. It also highlights limitations of the available methods and conditions that should be taken into account while designing a bio-relevant dissolution method for such systems.

Development and Validation of a Simple and Sensitive Spectrometric Method for Estimation of Cisplatin Hydrochloride in Tablet Dosage Forms: Application to Dissolution Studies

Cisplatin hydrochloride is an important chemotherapeutic drug for cancer treatment. It has a low molar absorptivity in the UV region and has no fluorescence. Therefore, a selective derivatizing reaction is required for its detection in bulk and pharmaceutical dosage form if detection by UV spectrophotometry is sought. In view of this, a simple, accurate, rapid, and cost-effective spectrophotometric method for its estimation has been developed by the complexation of the drug with ortho-phenylene diamine and monitoring the absorbance of formed green color at 706 nm. The method has been validated and successfully applied for the assay and dissolution studies of cisplatin hydrochloride tablets. The method demonstrated good linearity over the range from 0.4 to 1.4 μg/mL with a correlation coefficient of 0.9999. The accuracy of the method was 99.98%. The precision demonstrated relative standard deviation of less than 2.5%. The developed method was successfully applied for dissolution studies of sustained release tablets of cisplatin with a cumulative release of 86.7% in 12 hours. The proposed method can be applied in routine quality control in the pharmaceutical industries since it is precise, accurate, simple, and economic.

Stable amorphous binary systems of glipizide and atorvastatin powders with enhanced dissolution profiles: formulation and characterization

Abstract The aim of this study was to enhance the dissolution profile of the combination of glipizide and atorvastatin used for simultaneous treatment of hyperglycemia and hyperlipidemia. The strategy to formulate coamorphous glipizide–atorvastatin binary mixture was explored to achieve enhancement in dissolution. The coamorphous glipizide–atorvastatin mixtures (1:1, 1:2 and 2:1) were prepared by cryomilling and characterized with respect to their dissolution profiles, preformulation parameters and physical stability. Amorphization was found to be possible by cryomilling at various tried ratios of the two drugs. The data obtained from glass transition temperatures and from Raman spectroscopy point toward practically no interaction between the two drugs. The dissolution studies revealed the highest enhancement in dissolution profiles of cryomilled coamorphous mixtures containing GPZ:ATV in ratios 1:1 (B-5) and 2:1 (B-7). These two mixtures were, therefore, subjected to studies for the evaluation of precompression parameters in order to find their amenability to satisfactory compression into tablet dosage form. The selected formulation was found to be stable when subjected to accelerated stability testing at 40°. C/75% RH for six months as per ICH guidelines. Based on all these studies, it was concluded that GPZ:ATV (1:1) combination may be able to provide an effective therapy for the comorbidities of hyperglycemia and hyperlipidemia.

Study of regulatory requirements for the conduct of bioequivalence studies in US, Europe, Canada, India, ASEAN and SADC countries: Impact on generic drug substitution

Article history: In the last one decade, due to expiry of patented products as well as their exclusivity period, a drastic decline of branded pharmaceutical products and up streaming of generic drug market has been observed in developed as well as developing nations. This up rise in generic drug market is expected to rise in future till the arrival of new brand in market. This prevailing conditions could result in proliferation of generic drug manufacturing companies. The fact that generics do not undergo thorough extensive trials like innovator drugs, fuels further fears regarding their inferiority. Moreover, due to the hard competition amongst various companies to market their generics, the frequency of fraud and corruption have embarked doubts in consumers mind to reality. In order to blow away the doubts and re-establishing the credibility of generics in market, bioequivalence (BE) guidelines with stricter regulation should be the demand. The present study highlights the relevant regulatory guidelines for the conduct of bioequivalence studies in US, Europe, Canada, India, South Africa and South East Asian Nations. A comparative study of the differences in study design and specifications have also been addressed.

A novel dissolution method for evaluation of polysaccharide based colon specific delivery systems: A suitable alternative to animal sacrifice

The most extensively used test for predicting in-vivo release kinetics of a drug from its orally administered dosage forms is dissolution testing. For polysaccharide based, colon targeted oral delivery systems, the entire path of the gut traversed by the dosage form needs to be simulated for assessing its in-vivo dissolution pattern. This includes the dissolution testing sequentially in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and simulated colonic fluid (SCF). For SGF and SIF, simple and standardized composition is well-known. However, preparation of SCF requires addition of either the colonic contents of rodents or human faecal slurry. A method is proposed, wherein a mixture of five probiotics cultured in the presence of a prebiotic under anaerobic conditions is able to surrogate the colonic fluid. Release profiles of drug from colon targeted delivery systems in this medium were studied and compared to those generated in the conventionally used media containing rodent caecal contents and human faecal slurry. The results from the three studies were found to be quite similar. These findings suggest that the proposed medium may prove to be useful not only as a biorelevant and discriminatory method but may also help in achieving the 3Rs objective regarding the ethical use of animals.

Effect of co-administration of probiotics with polysaccharide based colon targeted delivery systems to optimize site specific drug release.

Significant clinical success of colon targeted dosage forms has been limited by their inappropriate release profile at the target site. Their failure to release the drug completely in the colon may be attributed to changes in the colonic milieu because of pathological state, drug effect and psychological stress accompanying the diseased state or, a combination of these. Alteration in normal colonic pH and bacterial picture leads to incomplete release of drug from the designed delivery system. We report the effectiveness of a targeted delivery system wherein the constant replenishment of the colonic microbiota is achieved by concomitant administration of probiotics along with the polysaccharide based drug delivery system. Guar gum coated spheroids of sulfasalazine were prepared. In the dissolution studies, these spheroids showed markedly higher release in the simulated colonic fluid. In vivo experiments conducted in rats clearly demonstrated the therapeutic advantage of co-administration of probiotics with guar gum coated spheroids. Our results suggest that concomitant use of probiotics along with the polysaccharide based delivery systems can be a simple strategy to achieve satisfactory colon targeting of drugs.

Patents on brain permeable nanoparticles.

The blood-brain barrier (BBB) presents a combination of physical and electrostatic barriers. It is a highly complex structure that tightly regulates the movement of molecules from the blood to brain, protecting it from injuries and diseases. However, the BBB also significantly precludes the delivery of drugs to the brain, thus, preventing the therapy of a number of neurological disorders like brain cancer, epilepsy, Alzheimers disease, schizophrenia etc. Numerous drug delivery strategies have been developed to circumvent this barrier. Out of those, one popular approach is the use of nanoparticles. Nanoparticles form solid, colloidal drug delivery system that consists of macromolecular materials in which the active principle is dissolved, entrapped or encapsulated or onto which the active principle is adsorbed or attached. Brain targeted polymeric nanoparticles have been found to increase the therapeutic efficacy and reduce the toxicity for a large number of drugs. By coating the nanoparticles with surfactants, higher concentrations of the drugs can be delivered. The article presents various approaches used in design and delivery of nanoparticles to brain. It also reviews various patents that describe the use of nanoparticles to deliver various neurotherapeutics to brain.