Drug Delivery Letters - Volume 8, Issue 2, 2018

Background: Nanoformulation strategies that render spatial placement and temporal delivery of drugs feasible, can be of utility in delivering the drug specifically to afflicted liver cells for greater therapeutic benefit. Receptor-based targeting is an excellent approach if the receptor is found exclusively on the cells to which drug needs to be delivered. Asialoglycoprotein receptors (ASGPR), mannose receptor, transferrin, glycyrrhetinic acid are some of the receptors selectively present on certain cell types within a liver. Objective: This review gives a glimpse of comparison of active vs. passive liver targeting and summarizes the plethora of ligands and delivery systems reported in the literature for targeting the receptors. Design of a targeted delivery system requires a comprehensive understanding of the interaction of targeting ligand with the receptors as well as its behaviour within the system. Discussion: The review highlights techniques like fluorescence correlation spectroscopy, confocal microscopy, flow cytometry and surface plasmon resonance as some in vitro tools that can aid in investigating the behaviour of targeted formulations with biological systems. The fate of delivery system via various endocytic mechanisms depending on the cell type has been outlined. Conclusion: Finally, the review deals with clinical relevance of liver-targeted nanoformulations addressing the aspect of safety and toxicity in developing targeted nanoarchitectonics.

Background and Objective: Amoebiasis, also known amoebic dysentery, is an infection caused by amoebas of the Entamoeba group. Symptoms may include abdominal pain, diarrhoea, or bloody diarrhoea. Complications can include inflammation of the colon with tissue death or perforation, which may result in peritonitis. People affected may develop anemia due to loss of blood. The purpose of present study was to develop Eudragit S100 coated colon targeted sustained release formulations of alginate-pectin and alginate-HPMC microbeads containing Norfloxacin (NF) and Tinidazole (TZ) for the treatment of amoebiasis. Methods: The formulations were prepared by ionotropic gelation method. Simultaneous estimations of Norfloxacin and Tinidazole were carried out spectrophotometrically at selected wavelengths of 273 and 310 nm. Optimized core beads of alginate-pectin were enteric coated with Eudragit S100. Formulations were evaluated for surface phenomenon, shape of beads, entrapment efficiency and in vitro drug release. Results: The average size of optimized alginate-pectin microbeads was found to be 881±0.05μm with an entrapment efficiency of 78.50±0.28% (NF) and 86.50±0.32% (TZ). The drug release was 71.16±0.45% (NF) and 80.63±0.56% (TZ) after 8 hr in phosphate buffer pH 6.8. Alginate- HPMC beads were of 902±0.02μm size with entrapment efficiency of 70.47±0.65% (NF) and 69.51±0.09% (TZ). The drug release was 66.95±0.55% (NF) and 73.37±0.43% (TZ) after 8 hr in phosphate buffer of pH 6.8. Enteric coating (10% weight gain) with Eudragit S100 of optimized alginate-pectin microbeads showed 73.15±0.54% (NF) and 81.59±0.56% (TZ) drug release in 12hr. The determined value of regression coefficients for zero order, first order and Higuchi models were found to be 0.777, 0.906 and 0.951, respectively. Conclusion: The formulated enteric coated sodium alginate and pectin microbeads may be taken orally to deliver Norfloxacin and Tinidazole specifically to the colon for effective treatment of amoebiasis. The approach described appears promising for the colonic delivery of drugs.

Background: Periodontitis is chronic bacterial induced infection capable of destroying tooth supporting tissues leading to pain, inflammation and tooth loss. Objective: The objective of the study was to optimize and evaluate Doxycycline Hyclate (DX) entrapped crosslinked chitosan microspheres by employing quality by design (QbD) for the treatment of periodontitis. Methods: Plackett-Burman Factorial Design was applied, and screening of significant factors was done by Pareto, half-normal and main-effect plots. The optimized batch was evaluated for FTIR, XRD, SEM, in-vitro drug release, swelling, and mucoadhesion. Cytocompatibility, antimicrobial, and stability studies were performed to prove its safety, efficacy and long-term utility respectively. Results: The responses like particle size, entrapment efficiency, and time for 80% of drug release was optimized at 75.45 μm, 88.87 % and 10.41 days respectively. FTIR reaffirmed formation of crosslinked microspheres. XRD plots indicated conversion of crystalline DX into amorphous form within microspheres. SEM evidenced spherical microspheres with smooth surfaces. Optimized microspheres showed slow and extended release for about fourteen days. Moreover, chitosan-vanillin (CSV) microspheres exhibited slow swelling with high mucoadhesion attributed to its high hydrophobicity and low degree of crosslinking than chitosan-glutaraldehyde (CSG) microspheres. SRB assay demonstrated high cytocompatibility of CSV than CSG microspheres against L929 cell lines. The optimized microspheres maintained a significant zone of inhibition against Staphylococcus aureus and Escherichia coli growth and showed prolonged stability for use. Conclusion: CSV microspheres showed great potential for their utility in chronic infections such as periodontitis by providing controlled and prolonged delivery of DX.

Background and Objective: In the present investigation, we have developed, optimized and evaluated a self-micro emulsifying drug delivery system (SMEDDS) of an anti-hypertensive drug valsartan. The objective of the study was to enhance dissolution rate, solubility and oral bioavailability of valsartan which is BCS-II class drug. Methods: Saturation solubility studies and emulsification tests were performed for selection of a suitable combination of oil, surfactant and co-surfactant. Pseudo-ternary phase diagram was constructed to estimate microemulsion region for selection of a required range of oil, surfactant and co-surfactant. Doptimal mixture design was utilized to optimize the concentration of various components used in the SMEDDS formulation and to analyze their effect on in vitro percent drug release and globule size. The effect of lipolysis on the rate of drug release from optimized SMEDDS formulation was calculated using in vitro lipolysis model. Result: The valsartan loaded SMEDDS formulation (F-14) containing 10% Capmul MCM PG 8 (oil), 40% Tween 20 (surfactant) and 50% Transcutol P (co-surfactant) was found to be optimized formulation with smallest globule size of 72.92 nm and significantly superior dissolution rate of valsartan in comparison to the pure drug. No major effect of lipolysis was observed on the diffusion rate of the drug from optimized SMEDDS formulation. Conclusion: Valsartan loaded SMEDDS formulation was successfully developed by using D-optimal mixture design that could potentially be used for improving the solubility, dissolution rate and bioavailability of Biopharmaceutical Classification System (BCS) class-II drugs.

Objective: The present study aims at optimizing, developing and evaluating the nail lacquer formulation for transungual delivery of ketoconazole for the management of onychomycosis. Methodology: Nail lacquer (NL) of ketoconazole was formulated using two different types of polymers i.e. hydrophobic (Eudragit RL 100) and hydrophilic polymer (Klucel LF; hydroxyl-propyl cellulose). The optimization of NL was done statistically using 32 full factorial design. Different polymer ratios (Eudragit RL 100/ Klucel LF; X1) and solvent ratios (ethanol/water; X2) were selected as independent variables. The formulations were evaluated for drying time (sec; Y2), drug permeation (μg/cm2/h; Y1) and peak adhesive strength (PAS) of NL film (g; Y3). The optimized formulation was then characterized for various parameters (non-volatile content, blush test, manual in vitro measurement of film adhesion) and by utilizing different techniques like ATR-FTIR, DSC and SEM. Ex vivo activity of the optimized formulation was assessed against Candida albicans (MTCC No. 3018). Results: The formulation having polymer ratio as 1:1 and solvent ratio as 90:10 was selected as the optimized formulation. The optimized NL formulation was observed to exhibit better penetration (~ 2.81 fold) as well as retention (~ 2.98 fold) in the animal hoof as compared to the marketed formulation. Ex vivo antifungal studies revealed that the antifungal activity of NL was ~1.25 fold greater than the marketed formulation and it further gets augmented in the presence of penetration enhancer. Conclusion: The findings of the present study evinced the developed NL as a promising vehicle for transungual drug delivery.

Background and Objective: The objective of the present investigation was to fabricate sustained release matrix tablets of carvedilol using different grades of HPMC and carbopol. Methods: Solid dispersion of carvedilol with PVP K30 was prepared using spray drying technique. This solid dispersion was incorporated into hydrophilic matrix of HPMC or carbopol in different ratios and directly compressed to get matrix tablets. The powder blend was characterized with bulk density, tapped density, Carr's compressibility index and Hausner ratio. Tablets were characterized for thickness, weight variation, hardness, drug content, in-vitro drug release and release mechanism. Results: Combination of HPMC K100M and HPMC K4M at concentration of 7.5% each in formulation could sustain the drug release for 18 h matching with marketed formulation and the drug release fitted to Higuchi's model for Fickian diffusion. Single grade of HPMC or carbopol or HPMC-carbopol combination did not match the target release profile. Flow property and compressibility of the powder blend was acceptable and suitable for direct compression process. Thickness, weight variation, hardness and drug content of the optimized tablet were well within the internationally accepted ranges. Conclusion: Combination of different grades of HPMC at appropriate ratios could match the release of carvedilol with the marketed product.

Background & Objectives: About 1.5 million people in the world suffer from Rheumatoid Arthritis (RA). Nearly three times as many women have the disease as men. Methods: Topical Thiocolchicoside Niosomal gel was formulated by thin film hydration method using molar ratio of Span 60: Cholesterol (X1), hydration volume (X2) and sonication time (X3) as independent variables and vesicle size (Y1) and entrapment efficiency (%EE)(Y2) as dependent variables. Results: 23 full factorial design was used and T3 batch was optimized which showed 80.5%EE, 244.3nm vesicle size and -34.4mV zeta potential indicating its stability. % In-vitro drug release study showed 93.12% drug release after 24hrs and was stable in refrigerated condition over 30 days. Preliminary batches of Niosomal gel were formulated by using different concentrations of Carbopol940 and HPMCK4M and from evaluation of gelling temperature and gelling time, C3batch was selected for the preparation of Niosomal gel which was formulated using optimized batch of niosomes and it exhibited pH 6-7, 85.55% CDR, pseudo plastic rheological behavior with good gel strength indicating the sustained release of drug and suitability of the formulation. Conclusion: Thus, thiocolchicoside niosomal gel might prove as promising drug carriers for pain management of RA through controlled drug release and increased topical retention time so to improve patient compliance with reduced dosing frequency and side effects.