Design, Optimization and Characterization of a Transferosomal Gel of Acyclovir for Effective Treatment of Herpes Zoster

A transferosome is the first generation of an elastic liposome prepared from phospholipids and edge activators. An edge activator is often a single-chain surfactant with a high radius of curvature that destabilizes the lipid bilayers of vesicles and increases the deformability of the bilayers, thereby making the vehicle ultra-deformable. Acyclovir is a synthetic purine nucleoside analog derived from guanine, is the most widely used antiviral agent. It is effective in the treatment of herpes simplex virus (HSV), mainly HSV-1 and HSV-2 and varicella-zoster virus. However, it has low skin permeability. Hence, the objective of this study was to prepare acyclovir using transferosomes to overcome the barrier function of the skin. The present study deals with the development of transferosomal gel containing acyclovir by handshaking method for painless acyclovir delivery for use in the treatment of skin disease through 33 Fractional factorial design in which amount of Phospholipid (A), Cholesterol (B) and Tween 80 (C) was selected as independent variables and vesicle size (X1) Polydispersity index (X2) and %entrapment efficiency (X3) as dependent variables. The prepared transferosomes were evaluated with respect to entrapment efficiency (EE %), particle size, and quantity of in vitro drug released to obtain an optimized formulation. The optimized formulation of acyclovir transferosomes was incorporated into a Carbapol 934 gel base which was evaluated for drug content, pH, spreadability, viscosity and in vitro permeation. The prepared acyclovir transferosomes had a high EE% ranging from 65 to 81%, with small particle sizes ranging from 181.9 to 401.8nm. The in vitro release study suggested that there was an inverse relationship between EE% and in vitro release. The formulation TF2 have better in-vitro drug release profile which contains carbopol 980 concentration 2 %w/w. The kinetic analysis of release profiles of TF2 was found to follow the Korsmeyer-Peppas model. All independent variables had a significant effect on the dependent variables (p-values < 0.05). Therefore, acyclovir in the form of transferosomes can penetrate the skin, overcoming the stratum corneum barrier. &nbsp

Formulation Development and Evaluation of Fast Dissolving Oral Film of Midodrine Hydrochloride

Oral fast dissolving midodrine hydrochloride films prepared by solvent casting method, PEG 400 was the selected plasticizers, incorporating superdisintegrants such as croscarmellose sodium (CCS) and sodium starch glycolate (SSG) to achieve the goal. Drug content, weight variability, film thickness, disintegration time, endurance, percentage of moisture content, and in vitro dissolution tests were analyzed for the prepared films. In all formulations, the tensile strength value was found from 0.965±0.045 and 1.256±0.032 and the folding capacity was over 100. The assay values ranged from 97.98±0.25 to 99.89±0.36 percent for all formulations. The disintegration time was ranging between 55±9 to 120±6 sec, the minimum time for disintegration was found in formulation F5 (55±9). The prepared F5 formulation shows greater release of the drug (99.25±0.41 percent) within 15 min relative to other formulations. As the drug having low solubility, fast disintegration may leads to more drug availability for dissolution, resulting in faster absorption in systemic circulation increased systemic availability of drug leads to quick onset of action which is prerequisite for hypertension. Keywords: Midodrine hydrochloride, Fast dissolving films, Solvent casting method, Superdisintegrants

Formulation and In Vitro Evaluation of Sustained Release Floating Matrix Tablet of Levofloxacin by Direct Compression Method

The objective of the present work was to develop Gastro retentive dosage forms which would remain in the stomach and upper part or GIT for a prolonged period of time thereby maximizing the drug release at desired site within the time before GRDFs left the stomach and upper part of the GIT, has provoked a great deal of increased interest in the formulation of such drug as floating drug delivery systems. Levofloxacin, (BCS class I) is a fluoroquinolone anti-bacterial agent. The rationale for the formulation of floating matrix tablet are acidic solubility of levofloxacin, residence of Halicobactor pylori mainly in sub region of stomach and the overdosing associated adverse effect due to continuous intake of drug in acute infection. A simple visible spectrophotometric method was employed for the estimation of levofloxacin at 294 nm and Beer’s law is obeyed in the concentration range of 2-10 μg /ml. Floating matrix tablet of levofloxacin was prepared by direct compression method using different polymers like hydroxyl propyl methyl cellulose (HPMC K4) and carbopol 934 as matrix formation polymers, sodium bicarbonate and citric acid was used as gas generating agents. The FTIR spectra of the levofloxacin and other excipients alone and in combination show the compatibility of the drug and excipients. Six formulations of different polymer percentages were formulated (F1-F6). Pre-compression parameters were evaluated. The influence of matrix forming agents and binary mixtures of them on levofloxacin release was investigated. The formulated tablets were characterized by hardness, friability, thickness, weight variation and in vitro drug release. The formulated tablets had acceptable physicochemical characters. The data obtained from the in-vitro dissolution studies of optimized batch F4were fitted in different models. The optimized formulation F4 showed 99.25% drug content and swelling index of 79.85 %. Drug release mechanism was found to be first order kinetics. Levofloxacin floating tablets exhibited increased gastric residence time, there by improved bioavailability and therapeutic effect of the drug. &nbsp

Phytochemical Screening and In Vivo Anti-inflammatory Activity of Hydroalcoholic Extract of Luffa acutangula (L) Roxb

Natural products are always helpful in the maintenance of life and good health. Luffa acutangula (L) Roxb (L. acutangula Cucurbitaceae) ranges from central and eastern Asia to south eastern Asia and is commercially grown for its edible unripe fruits, which are cooked and eaten as vegetable in Bangladesh and many parts of India. It is commonly known as ridge gourd, sponge gourd or angled luffa, Karviturai in hindi and dodake in marathi .The plant possesses various medicinal properties such as treatment of jaundice, splenic enlargement and laxative. Inflammation is a reaction of a living vascularised tissue to an injury. Conventional or synthetic drugs used in the treatment of inflammatory diseases are inadequate, it sometimes have serious side effects. So number of herbal medicines is recommended for the treatment of inflammation that has no side effects. The present study is aimed to evaluate the anti-inflammatory activity of L. acutangula on carrageenan-induced rat paw edema method in rats as for controlling inflammatory disorders. Acute toxicity of the extract (2000 mg/kg) was examined in wistar rats for 14 days. Qualitative analysis of various phytochemical constituents and quantitative analysis of total phenolics and flavonoids were determined by the well-known test protocol available in the literature. Phytochemical analysis revealed the presence of phenols, flavonoids, tannins, saponins, alkaloids ect. The total phenolics content of L. acutangula extract was (0.897mg/100mg), followed by flavonoids (0.765mg/100mg) respectively. Hydroalcoholic extract up to 2000 mg/kg did not produce any toxic effects. The hydroalcoholic extract of L. acutangula (100 and 200 mg/kg) inhibited the inflammation induced by carrageenan in rats in a dose dependent manner. The hydroalcoholic extract of L. acutangula possesses a strong anti-inflammatory activity and may be considered an interesting source of effective anti-inflammatory compounds. Keywords: Luffa acutangula (L) Roxb, Acute toxicity, Anti-inflammatory effect, Phytochemical screening, Flavonoid, paw edem

Phytochemical Screening and In Vivo Anti-inflammatory Activity of Hydroalcoholic Extract of Embelia Ribes Burm. F

Embelia ribes Burm. f. ( E. ribes,  Myrsinaceae), first described by Nicolaas Laurens Burman in 1768, is a woody climber distributed in the primary lowland and mountain forests of Bangladesh, Burma, Cambodia, India, Laos, peninsular Malaysia, Thailand and Vietnam. Ayurvedic medicine prescribes the dried fruits or vidanga and used as antibacterial, antifertility activities, antiprotozoal, abdominal disorders, lung diseases, constipation, indigestion, fungus infections, mouth ulcer, sore throat, pneumonia, heart disease, obesity, analgesic, anti-inflammatory and antioxidant. Inflammation is a reaction of a living vascularised tissue to an injury. Conventional or synthetic drugs used in the treatment of inflammatory diseases are inadequate, it sometimes have serious side effects. So number of herbal medicines is recommended for the treatment of inflammation that has no side effects. The present study is aimed to evaluate the anti inflammatory activity of E. ribes on formalin induced paw edema in rats as for controlling inflammatory disorders. Acute toxicity of the extract (2000 mg/kg) was examined in wistar rats for 14 days. Qualitative analysis of various phytochemical constituents and quantitative analysis of total phenolics and flavonoids were determined by the well-known test protocol available in the literature. Phytochemical analysis revealed the presence of phenols, flavonoids, tannins, saponins, alkaloids ect. The total phenolics content of E. ribes extract was (1.155mg/100mg), followed by flavonoids (0.811mg/100mg) respectively. Hydroalcoholic extract up to 2000 mg/kg did not produce any toxic effects. The hydroalcoholic extract of E. ribes (100 and 200 mg/kg) inhibited the inflammation induced by formalin in rats in a dose dependent manner. The results of present study demonstrate that hydroalcoholic extract of the seeds of E. ribes possess significant (P < 0.05) anti-inflammatory potential. Keywords: Embelia ribes Burm. f, Acute toxicity, Anti-inflammatory effect, Phytochemical screening, Flavonoid, paw edem

Formulation, Development and Evaluation of Bilayer Floating Tablet of Gemfibrozil

Formulation development is an important part of drug design and development. Bioavailability and bioequivalence are totally dependent on formulation development. Now-a-days formulation development is done by following QbD (Quality by Design).The aim of present study is to formulate Gemfibrozil (Gem) sustained release (SR) and immediate release (IR) bilayer tablet by different concentration of Hydroxypropyl methylcellulose (HPMC) and HPMC K 100 M to control the release pattern. The sustained release layer of Gem was prepared by using different grades of HPMC like, HPMC K-15, HPMC K-4 along with other excipients by direct compression technique. The immediate release layer of Gem was prepared by Cross carmellose sodium, Crospovidone and Sodium starch glycolate by direct compression technique. The powders were evaluated for their flow properties and the finished tablets were evaluated for their physical parameters. The both immediate release and sustained release layers of Gem were characterized by FT-IR and in vitro dissolution studies. The drug release study of Gem was evaluated using USP-II paddle type dissolution apparatus. The release rate of Gem in immediate release layer was studied for 15 min in 0.1 N HCL media and that of Gem in sustained release layer was studied for 12 h in 0.1 N HCL. From the nine batches F6 batch showed good release behaviour 99.85% of drug is released over 12 hours. Gem belongs to BCS Class II (log P 3.6) with poor solubility and high permeability resulting in limited and variable bioavailability. Total four trial batches of each drug have been manufactured to optimize and develop a robust and stable formulation, the stability studies of the products also comply with ICH guideline. Keywords: Bilayer floating tablets, Gemfibrozil, Biphasic drug release, HPMC K 15

CHARACTERIZATION OF BI-LAYERED TABLET FOR TREATING HEPATOTOXICITY CAUSED BY ANTITUBERCULAR DRUG FOR THE EFFECTIVE MANAGEMENT OF TUBERCULOSIS.

The proposed study aimed at development and characterization of bi-layered tablet for treating hepatotoxicity caused by antitubercular drug for the effective management of tuberculosis. Isoniazid is first line antitubercular drug which acts via inhibiting InhA and KasA genes. Based on its solubility and log P values, drug was found to be hydrophilic in nature. Isoniazid is first line drug due to its high efficacy but major disadvantage associated with this drug is hepatotoxicity. Due to this drawback there are various chances to discontinue the therapy. Hence, to prevent this discontinuation silymarin, a herbal hepatoprotective drug can be used in combination with isoniazid. Isoniazid was obtained as white, crystalline powder and its melting point was found to be in 161ºC-164º C range. It has maximum absorbance at 261nm and endothermic DSC peak at 163ºC. Based on solubility profile and log P value, amphiphilic nature of Silymarin was determined. Silymarin was obtained as solid powder with maximum absorbance at 288 nm The drug content of bilayer tablet was estimated by simultaneous estimation method. Bilayer tablet was prepared by using HPMC, Carbopol, and cyclodextrin in optimum concentration. Prepared bilayer tablet was optimized for in vitro drug release in altered media. Then the formulation with higher sustained release was selected for bilayer tablet formulation. Bilayer tablet was characterized on the basis of different parameters such as hardness, friability, weight variation, drug content and in vitro drug release. Drug release kinetics of silymarin from bilayer tablet was found to be Hixson Crowell mechanism whereas INH followed Higuchi diffusion model. Key words: hepatotoxicity, antitubercular , tuberculosis, Isoniazid, amphiphilic nature