Drug Delivery Letters - Volume 3, Issue 2, 2013

Multiple-unit type oral modified drug delivery system of aceclofenac was developed by ionotropic gelation method for targeted drug delivery and to reduce the chances of side effects. Various batches of microspheres were developed by ionotropic gelation method using single and blends of polymers. Along with usual physical properties, the microspheres were also subjected to enteric nature, in-vitro drug release and mucoadhesion studies to investigate a possible sustained drug release and their use in in-vivo as a gastro-protective system for aceclofenac. It was observed that prepared microspheres could be able to restrict the drug release in stomach region and prolong the drug release by adhering on to the intestinal mucosa. In vitro drug release suggested a combination of drug diffusion and spheres erosion could be the release mechanism and it was also found that blend of polymers is more effective in sustaining the drug release than either polymer. Optimized microsphere formulation suggested 71.03 ± 4.94 % edema inhibition at 12 hours and shelf life of about 2.32 years at room temperature. Algino-gelatin multiunit dosage system exhibits promising properties for once daily targeted release form of aceclofenac in order to reduce the side effects and enhance the patient’s compliance.

The objective of this study was to prepare gastro-retentive microcapsules using solvent evaporation method containing salbutamol sulphate. The effect of various viscosity grades of ethylcellulose (EC) on In vitro drug release and buoyancy was evaluated. The influence of formulation factors (stirring speed, Drug: EC ratio, various viscosity grades of EC) on particle size, encapsulation efficiency, in-vitro release characteristics was studied. FT-IR and DSC studies revealed no interaction between drug and EC. The yields and the encapsulation efficiencies were high for all microcapsule formulations. Floating lag time was zero for all microcapsules prepared with EC 7 cPs whereas EC N50 based microcapsules did not show buoyancyl. EC 18-22 cPs based microcapsules showed zero floating lag time for formulations with drug to EC ratio of 1:1 and 1:1.5 but 1:2 ratio did not exhibit buoyancy. Stirring speed was inversely related to the size of the microcapsules. In-vitro release studies revealed that the drug release was sustained upto 12 h for microcapsules prepared with EC 18-22 cPs and EC N50 whereas EC 7 cPs based microcapsules could not sustain the release for more than 6 h. Stability studies as per ICH guidelines revealed no significant change in drug entrapment efficiency, in vitro buoyancy and in vitro drug release. Hence incorporation of optimum concentration of EC 18-22 cPs (F5) in the formulation of microcapsules by solvent evaporation method proved to be an effective method in achieving desired release behavior and buoyancy.

Background and Purpose of Study: Simvastatin (SIM) is a 3-hydroxy-3methylglutaryl-coenzyme A (HMG Co-A) reductase inhibitor that is insoluble in water. Its low water solubility rate limits the pharmacological effects. Pluronic F68, a hydrophilic polymer is known for its hepatic CYP3A4 enzyme inhibition. CYP3A4 is the key enzyme for the metabolism of SIM in liver. The aim of the present study was to improve solubility, dissolution rate and antihyperlipedimic activity of SIM using solid dispersion with pluronic F68. Methods: The solid dispersions in different w/v ratio were prepared by solvent evaporation method. The solid dispersions were evaluated for drug content, saturation solubility, in vitro dissolution rate and for their in vivo antihyperlipedimic activity. The probable drug polymer interactions were studied by fourier transform infrared (FTIR) spectroscopy. Results and Major Conclusions: Probable machanisms of improved solubility and dissolution were characterized by Differential Scanning Calorimetry (DSC) and Powder X-ray diffractomery (PXRD) of drug and solid dispersions. This study revealed that preparation of solid dispersion of SIM with pluronic F68 is not only improving the dissolution of SIM but also enhancing its antihyperlipedimic activity.

Optimization of experiments, such as those used in drug discovery is useful for saving scientific resources. As bioavailability, practical mass production criteria of process and product reproducibility are foremost requirements of any final product and to meet these requirements optimization of production process is a necessary step. The main goal of this chapter is to provide different approaches of optimization and important features, strengths and limitations of optimization techniques like factorial design, Taguchi design, response surface methodology, simplex lattice design that used for the optimization of fast dissolving drug delivery systems. Factorial design is the design of choice for simultaneous determination of the effect of several factors and their interactions while Taguchi method reduces the variation in a process through robust design of experiments. Response surface methodology is a collection of statistical and mathematical techniques useful for developing, improving and optimizing processes. Simplex lattice can be used to determine the relative proportion of ingredients and optimizes a formulation with respect to specified variables.

Drug targeting is delivery of drug to receptor, organ or any other specific part of body exclusively. Delivery of the drug by the oral route remains the most important route for the administration of medicines to patient. This manuscript highlights organ of digestive system (colon), their size and physiology and transit pattern of dosage forms while travelling through digestive tract. The colon is a site where both local and systemic delivery of drugs can be given. Targeted drug delivery into the colon is highly desirable for local treatment of a variety of bowel diseases such as ulcerative colitis, crohn’s disease and colonic cancer. However the drug can be targeted directly into the colon to reduce the systemic side effects. Precise colon targeted drug delivery requires that the triggering mechanism in the delivery system should only respond to the physiological conditions particular to the colon. Hence, continuous efforts should be focused on designing colon-specific delivery systems with improved site specificity and drug release kinetic to accommodate different therapeutic needs. This review mainly compares different strategies for colon specific drug delivery such as prodrug and polymeric prodrug, which achieved limited success and have limitations as compared with novel colon specific drug delivery systems namely pressure, time, pH and bacteria dependent, chitosan-calcium alginate microparticles, microsponges, nanospheres, nanoparticles, osmotic controlled systems. These novel systems are unique in terms of achieving in-vivo site specificity and feasibility of manufacturing process. The in-vivo evaluation includes various techniques for colon specific drug delivery system such as string technique, endoscopy, radiotelemetry, roentgenography and gamma scintigraphy.

Optimization studies on mucoadhesive microspheres of felodipine for nasal delivery were aimed to modulate drug release, enhance residence time of microspheres and thereby improve the therapeutic efficacy of the drug undergoing extensive first pass metabolism. Mucoadhesive sodium alginate microspheres containing felodipine were prepared by emulsion-cross linking method. A 23 factorial design was employed for preparation of microspheres wherein the concentration of polymer, concentration of calcium chloride and cross-linking time were chosen as independent variables while particle size, % mucoadhesion and % drug permeation were taken as dependent variables. Amongst the cross-linking agents screened, calcium chloride was selected on the basis of particle size, regular shape and percentage yield. The microspheres, formulation F3 with least particle size of 39.9 µm, maximum in vitro mucoadhesion 79.98% and % drug permeation 94.8% were adjudged as optimized formulation. The experimental design was validated by extra design check point. SEM revealed the morphological characteristic of microspheres. DSC and XRD confirmed molecular dispersion of the drug in the microspheres polymeric matrix. DRS revealed no chemical interaction between the drug and polymer used. Histological study asserted no damage to the sheep nasal mucosal structure when incubated with F3. The formulation was found to be stable for a period of 3 months.

Epigenetic modifications, such as DNA methylation and histone acetylation, are well established as important players in tumourigenesis and thereby sought after targets in therapeutic intervention. Recent years have seen an increase in the research and clinical development of histone deacetylase (HDAC) inhibitors as anti-cancer agents, but emerging evidence now suggests that the class of enzymes performing the reciprocal function of histone acetylation, histone acetyltransferases (HATs), may also have pivotal roles in cancer progression. Here we discuss the role of HAT complexes in tumourigenesis and their potential as bona fide druggable cancer targets, focusing in particular on the evolutionary conserved TIP60 complex.