Current Drug Therapy - Volume 11, Issue 2, 2016

Background: Topical drug delivery system is an attractive way to target dermatological disorders. Dapsone is commonly used as anti-leprotic drug. In this research work dapsone was repurposed for treating acne via topical application. Objective: The aim of present work was to formulate, optimize and characterize hybrid nanoparticles (HNs) containing DAP (dapsone) and incorporating the same into a topical gel base. Method: The HNs were prepared using melt-emulsification and ultrasonication process. The HN formulations were characterized for particle size, zeta potential and entrapment efficiency applying 23 factorial design. Results: The results revealed that HN-4 has an average particle size of 277nm, zeta potential of -26.7 mV, entrapment efficiency of 75.81%. Transmission electron microscopy (TEM) confirmed that HNs were spherical in shape with polymer core surrounded by a lipid shell. Further, the pelletized HNs were incorporated in carbopol 940 gel base and analysed for pH, drug content, viscosity and optimized batch was evaluated for texture analysis, in-vitro skin permeation, and antimicrobial study. The stability studies showed that DAP-HN4 G3 (dapsone loaded carbopol gel) stored at 40±2oC was stable and non-irritant as per Hen’s Egg Test Chorioallantoic Membrane (HET CAM) study. Conclusion: It can be concluded that formulation containing DAP HNs was found to be stable, non-irritant and may prove to be an effective and promising delivery system for acne treatment.

Background: Glycyrrhetinic acid ammonium (GAA) inhibits the biosynthesis of prostaglandins PGE-2 and PGF-2α to their inactive metabolites. This causes an increased level of prostaglandins in the digestive system which inhibit gastric secretion. Objective: The aim of the present investigation was to develop mucoadhesive microspheres of GAA using Colocasia esculenta (CE) and Bombax ceiba (BC) mucilages, alone and in combination for the efficient treatment of gastric ulcer. Methods: The glycyrrhetinic acid (GA) was extracted as ammonium salt from dried stolons of Glycyrrhiza glabra using hot maceration technique. Extraction of mucilage was carried out using herbs and rhizomes of CE and flowers of BC by cold maceration method. The hydrophilic molecule of GAA was encapsulated using single phase emulsification technique. Glutaraldehyde was used as cross-linking agent. The developed microspheres were evaluated for morphology, particle size, entrapment efficiency, drug loading, in vitro mucoadhesion, swelling behavior, in vitro drug release and in vivo ulcer healing activity. Results: The results showed that the drug-polymer in 1: 2 ratio in CE- mucilage containing microspheres exhibited prolonged drug release as compared to BC-mucialge or their combination. The stability study results showed stable character of GAA in the developed microspheres. The developed microspheres show effective in vivo ulcer healing activity in Wistar male albino rats. Conclusion: The preliminary results of this study suggest that the developed mucoadhesive microspheres containing GAA could be a promising tool in the treatment of gastric ulcer and can be advantageous over the conventional anti ulcer therapy. The study also suggested that the extracted mucilages can be used in the preparation of the mucoadhesive microspheres.

Background: Colocasia esculenta is a fast growing plant and is cultivated for consumption of leaf and tuber. Polysaccharide obtained from the tubers of Colocasia esculenta is known as Taro polymer. Chemically it is neutral heteropolysaccharide of galactose, galactose and arabinose. Objective: The present research work was aimed at the development and characterization of orally disintegrating tablet of Valsartan using natural disintegrant to produce rapid onset of action and patient compliance. Method: Polysaccharide from Colocasia esculenta tubers was isolated using solvent precipitation method. The isolated polysaccharide was investigated as disintegrant in orally disintegrating tablets. Valsartan, an antihypertensive drug, was selected as a model drug. The drug excipient interactions were characterized by FTIR studies. The tablets of Valsartan were prepared separately using different concentrations [2.5, 5, 7.5 and 10 % w/w] of isolated Colocasia esculenta polysaccharide and Kollidon®, Ac-Di-Sol® as synthetic superdisintegrants by using direct compression method. The tablets thus prepared were evaluated for various pre-compression and post-compression parameters. The disintegration time and in vitro drug release of the optimized formulation was compared with the available marketed formulation. The stability studies were performed on the optimised batch F12. Results: The formulation F12 containing 10 % of polysaccharide showed rapid wetting time and disintegration time and is comparable to formulations prepared using synthetic superdisintegrants at the same concentration level. Conclusion: Colocasia esculenta polysaccharide can be used as a disintegrant in the formulation of orally disintegrating tablets. Its disintegrating property was found to be comparable with that of the commercially available superdisintegrants.

Background: Treatment of fungal infection through oral route is avoided since topical delivery has ease of application and improved patient compliance. Topical drug delivery is used for local administration of drug directly to the affected area, resulting in localization of drug. Objective: The objective of the present study was to prepare and evaluate fluconazole (FLZ) loaded microemulsion (ME) based gel for topical delivery. Methods: Triacetin as the oil phase, tween 80 as surfactant and ethanol as cosurfactant were screened as microemulsion components. Pseudoternary phase diagrams were constructed by titration method and various MEs was prepared and evaluated for parameters like globule size, poly dispersibilty index (PDI), viscosity, pH, and stability. Finally, optimized microemulsion (ME9) was selected to prepare various gels and evaluated for drug content, viscosity, pH and spreadability. Optimized microemulsion based hydrogel containing carbopol 934 (MBH6) was compared with marketed formulation or ex vivo permeation study using rat skin. The optimized MBH6 and marketed formulation were also evaluated for antifungal activity against fungal strain Microsporum fulvum (MTCC 16446) as well as for skin irritation studies. Results: The studied optimized MBH6 showed a good stability over a period of 6 months. The average globule size of optimized ME9 was found 36.17 nm. The antifungal activity of MBH6 was found comparable to the marketed formulation. Conclusion: It was concluded that the proposed microemulsion based hydrogel (MBH6) is a promising delivery vehicle for topical delivery of FLZ.

Background and Objectives: Microcos paniculata is widely distributed throughout the Bangladesh which belongs to the family Tiliaceae. The present study was considered to determine anti-diarrheal, analgesic, membrane stabilizing and thrombolytic activities with evaluation of phytochemical nature of methanolic extract of M. paniculata steam bark. Methods: Methanolic extract of this plant part was prepared at room temperature and the concentrated methanolic extracts used for the phytochemical screenings by using appropriate and proper procedure for the investigation of phytoconstituents. The extract was then used for investigation of in-vitro thrombolytic and membrane stabilizing activity. The in-vivo antidiarrheal and analgesic activities were done according to the method of castor oil and acetic acid induce writhing respectively. Results: Phytochemical study reveal the presence of flavonoids, diterpenes, alkaloids, saponin, tannin and phenols. During the estimation of anti-diarrheal activity plant extract showed most significant inhibition of 63.30% and 56.70% diarrhea at 400 mg/kg and 200 mg/kg, respectively. Analgesic test showed pain inhibition of 41.36% and 32.0% at 500 mg/kg and 250 mg/kg, respectively in contrast to standard drug (Ibuprofen) showed 46.64% inhibition of pain. The membrane stabilizing study showed that the inhibition of hemolysis increases respectively when the dose increased. Similar result was found in thrombolytic activity which means that when the dose increased, the thrombolytic activity of the plant extract increased. Conclusion: By considering this result, it can be concluded that M. paniculata may lead to find novel drugs for cardiovascular and diarrheal patient and also bring hope for patients suffering with diverse pain.

Objective: Interpenetrating polymer network (IPN) hydrogel beads have been prepared for the controlled release of theophylline. Method: Theophylline loaded IPN hydrogel beads of casein and sodium carboxymethyl xanthan (SCMX) were prepared by simple ionotropic gelation and covalent crosslinking method in an aqueous environment. Hydrogel beads were characterized by Differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and Scanning electron microscopy (SEM). Release of drug from beads has been investigated in pH 1.2 KCl/HCl buffer and pH 6.8 phosphate buffers. Results: Release of drug from beads has been investigated in pH 1.2 KCl/HCl buffer and pH 6.8 phosphate buffers. All the formulations exhibited slow drug release in pH 1.2 KCl/HCl buffer and the maximum drug release in 2 h was 20.45±0.31 %. The dissolution profiles of theophylline in phosphate buffer solutions (pH 6.8) from hydrogel beads also showed retarded release pattern. Retardation of drug release was observed with increasing casein concentration, glutaraldehyde (GA) concentration, and drug loading. However, increasing aluminium chloride (AlCl3) concentration showed a quicker drug release. Drug release from hydrogel beads followed Fickian and anomalous transport in both the dissolution medium. Conclusion: Sodium carboxymethyl xanthan and casein cross-linked with Al3+ and GA could be an appropriate matrix for the preparation of interpenetrating polymer network hydrogel beads for controlled release of theophylline.

Background: More than 90% of cancer deaths are caused by cancer metastasis. Cancer metastatic therapy is a top priority topic. Objective: New therapeutics against cancer metastasis is to be discovered. Methods: In the past pathogenesis study, a therapeutic dilemma has been discovered from literatures of epithelial-mesenchymal cell interchange in late-staged cancer patients—opposite tumor pathogenesis routes between primary and metastatic tumors. Results: Possible options for overcoming this dilemma are enlisted from different therapeutic attempts (such as novel drug target (cancer biomarkers) discovery, antimetastatic drug developments, biotherapies, drug combinations, cancer therapeutics according to metastatic cascades, different types of personalized medicine paradigms and so on). Conclusions: These therapeutic options might change the landscape of cancer treatments and managements in clinics forever.