Formulation Development and Evaluation of Itraconazole Loaded Invasomes Hydrogel

Topical drug administration is a localized drug delivery system anywhere in the body through ophthalmic, rectal, vaginal and skin as topical routes. Skin is one of the most readily accessible organs on human body for topical administration and is main route of topical drug delivery system. There are various skin infections caused by fungus. An antifungal medication is a pharmaceutical fungicide used to treat mycoses such as athlete’s foot ringworm, candidiasis. Antifungal works by exploiting differences between mammalian and fungal cells to kill the fungal organism without dangerous effect on host. Itraconazole (ITZ) is commonly used in the treatment of fungal infections. It has low bioavailability (55%) because of low aqueous solubility and first pass effect. Hence we attempted to develop Itraconazole-loaded invasomes hydrogel. ITZ-loaded invasomes were prepared by conventional thin layer evaporation technique using Phospholipon 90H, terpene (Limonene) and ethanol. The optimized ITZ-loaded invasomes was incorporated into carbopol 934p (0.5 to 2%) solution to get a hydrogel for improving convenience in superficial application. FT-IR studies revealed no interaction between the drug and excipients. The formulated hydrogel formulation was evaluated with parameter pH, viscosity, gel strength, drug content, spread ability, in-vitro release test, wash ability, extrudability study and stability studies. The formulation OIGF4 showed a drug content of 99.12% and drug release of 99.78% in 72 hrs, which contains carbopol 934p concentration 2%w/w. The present work also focuses on making the formulation more pharmaceutically acceptable.

Development and characterization of effervescent floating tablet of famotidine for treatment of peptic ulcer

Floating drug delivery systems (FDDS) are utilized to target drug discharge in the stomach or to the upper parts of intestine. Famotidine has been the most extensively used drug for the management of peptic ulcer for various decades. The current study concerns the development and evaluation of floating tablets of famotidine which, after oral administration, are planned to extend the gastric residence time, enhance drug bioavailability and aim the gastric ulcer. A FDDS was expanded using gas-forming agents, like sodium bicarbonate, citric acid and hydrocolloids, like hydroxypropyl methylcellulose (HPMC) and carbopol 934P. The prepared tablets were evaluated in terms of their pre-compression parameters, physical characteristics, buoyancy, buoyancy lag-time, in vitro release, and swelling index. The formulations were optimized for the different viscosity grades of HPMC, carbopol 934P and its concentrations and combinations. The consequences of the in vitro release studies demonstrated that the optimized formulation (F6) could sustain drug release (98%) for 24 h and remain buoyant for 24 hr. Optimized formulation (F6) showed no considerable change in physical appearance, drug content, total buoyancy time or in vitro dissolution study after storage at 40°C/75% RH for 3 months. Lastly the tablet formulations establish to be economical and may conquer the draw backs associated with the drug during its absorption. Keywords: Famotidine, Floating drug delivery system, Hydrocolloids, Gastric residence time.

Emulgels Containing Propolis and Curcumin: The Effect of Type of Vegetable Oil, Poly(Acrylic Acid) and Bioactive Agent on Physicochemical Stability, Mechanical and Rheological Properties

Emulgels are obtained by the entrapment of an organic phase within a three-dimensional network built by hydrophilic molecules. Polymers based on cross-linked poly(acrylic acid) have been utilized as gel matrices, improving adhesiveness, rheological and mechanical performance. Propolis (PRP) produced by Apis mellifera L. bees displays a wide range of biological activities. Together with curcumin (CUR), they may show synergic anti-inflammatory, antioxidant and antimicrobial action on skin disorders. This work investigated the effect of vegetable oils (sweet almond, andiroba, and passion fruit) with regard to the physicochemical properties of emulgels composed of Carbopol 934P®, Carbopol 974P®, or polycarbophil aiming the CUR and PRP delivery. Physicochemical stability enabled the selection of systems containing passion fruit or andiroba oil. Mechanical and rheological characteristics provided rational comprehension of how vegetable oils and bioactive agents affect the structure of emulsion gels. All formulations exhibited high physiochemical stability and properties dependent on the polymer type, oil, and bioactive agent. Formulations displayed pseudoplastic, thixotropic and viscoelastic properties. Emulgels containing andiroba oil were the most stable systems. Carbopol 934P® or polycarbophil presence resulted in formulations with improved smoothness and mechanical properties. Systems containing andiroba oil and one of these two polymers are promising for further investigations as topical delivery systems of CUR and/or PRP on the skin and mucous membranes.

Formulation by Design (FbD) approach to develop pharmaceutically amended Diclofenac Sodium hydrogel as compared to marketed gel

The aim of the present study was to develop pharmaceutically better performing Diclofenac Sodium hydrogel through FbD approaches as compared to marketed gel. The quality target product profile was set for the critical quality attributes of the gel. The key material variables like Carbopol 934P, propylene glycol and Triethanolamine (TEA) were optimized using design of experiments. A response surface central composite design was used considering viscosity, pH and cumulative percentage permeation of the drug up to 120 min as responses. TEA had a significant effect on the pH at concentrations of 0.3182-3.6818% (w/w). The applicability of the optimized formulations was influenced by both Carbopol 934P (0.6591-2.3409%; w/w) and propylene glycol (PG; 6.591-23.409%; w/w) content due to their ability to alter the formulation viscosity. The optimized formulation, determined mathematically, contained 1.5% (w/w) Carbopol 934P. 2.0% (w/w) TEA and 15% (w/w) PG. The optimized hydrogel and marketed gel were evaluated for viscosity, spreadability, skin irritation, homogeneity and grittiness, texture analysis, in vitro release and ex vivo permeation studies. When these evaluation parameters were compared with a marketed gel in respect of all the evaluating tests, the optimized hydrogel was found to be far better formulation than the marketed one.

FORMULATION AND EVALUATION OF IN-SITU GEL CONTAINING LINEZOLID IN THE TREATMENT OF PERIODONTITIS

Objective: The intent to prepare and evaluate Linezolid in-situ gel in the treatment of periodontitis. Methods: pH-sensitive in-situ gel was formed by the cold method using a varying concentration of the drug, carbopol 934P and hydroxypropyl methylcellulose (HPMC) and carbopol 934P and sodium carboxy methylcellulose (CMC) (1:1,1:1.5,1:2,1:2.5). An optimized batch was selected based on gelling time and gelling capacity. The prepared in-situ gels were evaluated for appearance, pH, gelling capacity, viscosity, in vitro release studies, rheological studies, and finally, was subjected to drug content estimation and antibacterial activity test. Results: FTIR study shows drug and physical mixture were compatible with each other. The rheology of formulated in-situ gel exhibited a pseudoplastic flow pattern. this may be because when polymer concentration was increased the prepared formulations become more viscous and in turn delayed the drug release and from the prepared formulation, LF4 and SF4 have polymer concentrations i. e, 0.9% carbopol and sodium CMC showed drug release up to 12 h. Conclusion: When carbopol is appropriately mixed with other suitable polymers it forms an in-situ gel-forming system that was substantiated by the property to transform into stiff gels when the pH is increased. The in-situ gel was prepared using a combination of carbopol-HPMC and carbopol-Na CMC The formulations LF1 to SF4 showed high linearity (R2 = 0.490-0.682), indicating that the drug was released from the prepared in-situ gel by the diffusion-controlled mechanism. Thus, the formulation of batches LF4 and SF4 containing carbopol: HPMC and carbopol: NaCMC in 1:2 ratios were considered as optimum formulation based on optimum viscosity, gelling capacity and to extend the in vitro drug release.

Formulation, Ex-Vivo and Preclinical In-Vivo Studies of Combined pH and Ion-Sensitive Ocular Sustained In Situ Hydrogel of Timolol Maleate for the Treatment of Glaucoma

The aim of the present research work was to develop safe, effective, and stable in situ hydrogel for the ophthalmic drug delivery using the combination of ion-responsive polymer gellan gum and pH-sensitive polymer carbopol 934P to treat glaucoma. Background: Timolol maleate is a BCS class I drug used as the first line of treatment in open-angle glaucoma. The rapid precorneal elimination of conventional formulation containing class I drugs exhibits poor therapeutic effect and bioavailability. So, in situ gelling system was formulated and characterized. Methods: Box-Behnken design was used to statistically optimize the formulation parameters and evaluate the effects of formulation attributes, namely concentration of gellan gum (X1), the concentration of carbopol 934P (X2) and concentration of benzododecenium bromide (X3) on selected critical quality attributes (Y1-Y7). Trial run data were statistically analyzed using the polynomial equation and response surface plots. Optimized formulation was selected based on desirability function, design space, and was further characterized and compared with the marketed formulation. Results: The concentration of both polymers showed a synergistic positive impact on viscosity at the non-physiological and physiological conditions. Trial runs showed controlled drug release with diffusion-controlled mechanism and good mucoadhesive strength due to the presence of Carbopol 934P. The preservative benzododecenium bromide showed the ability to enhance trans-corneal permeation. The optimized formulation has appeared as a clear solution at the non-physiological condition and clear gel at the physiological condition with an acceptable pH range of 5-6. Other quality attributes like rheological properties, gelling capacity, texture analysis, Isotonicity, contact angle, sterility, antimicrobial efficacy, and stability were found in desires values for the ocular application. The safety of in situ gel for human use was confirmed by ocular irritation and histopathology studies in the rabbit eyes. The intraocular pressure (IOP) reduction with optimized formulation was found comparable and less fluctuating compared to ophthalmic gel-forming marketed solution of timolol maleate (TIMOPTIC-XE®). Conclusion: The cross-linking between Carbopol 934P with Gellan gum in the formation showed more viscous gelling at the physiological condition to provide long pre-corneal residence time. The optimized formulation exhibited all the desirable attributes of an ideal ophthalmic in situ gelling formulation, exhibited in-vitro controlled drug release, good gelling capacity, and was found to be stable and non-irritant to the eye.

Quality and Release Profile of Captopril from Mucoadhesive Gastroretentive Tablet by Using Matrix Sodium Carboxymethyl Cellulose and Carbopol 934P

Captopril have good absorption in gastric pH and ionized on intestinal pH. It is necessary to keep the drug in the form of molecules in the area of the absoption. The mucoadhesive gastroretensive drug delivery system provides the possibility of controlled release in stomach in a certain amount of time. Research has been conducted to assess the quality and profile of captopril release in of a mucoadhesive gastroretensive tablet. Mucoadhesive tablets (MK) were made in 5 formulas by wet granulation method using carbopol 934P and sodium carboxymethyl cellulose as matrix with ratio 10: 0 (MK1), 0: 10 (MK2), 5: 5 (MK3), 7: 3 (MK4), and 3: 7 (MK5). The parameters which was evaluate were characteristics of granules and tablets and kinetics model of captopril release from tablets in 0,01 N HCl medium. Mucoadhesive tablets had different characteristics for each formula. Mucoadhesive tablets that had good quality and release profile were shown by MK4 and MK5 formula. They had controlled drug release profiles accorded to the Korsmeyer-Peppas and Higuchi kinetics models, respectively.

CYCLODEXTRIN DERIVATIVE ENHANCES THE OPHTHALMIC DELIVERY OF POORLY SOLUBLE AZITHROMYCIN

Azithromycin (AZM), a macrolide antibiotic used for the treatment of Chlamydial conjunctivitis, is less effective for the treatment of this disease due to its poor bioavailability (38%). Various alternatives have been developed for improving the physico-chemical properties (i.e., solubility) of the AZM without much success. To overcome the problems associated with AZM, an inclusion complex employing a modified cyclodextrin i.e., sulfobutylether-β-cyclodextrin (SBE-β-CD) was prepared and characterized by phase solubility studies, pXRD and FTIR techniques. The results portrayed the formation of the inclusion complex of AZM with sulfobutylether β-cyclodextrin (SBE-β-CD) in 1:2 molar stoichiometric ratios. This inclusion complex was later incorporated into a polymer matrix to prepare an in situ gel. Various combinations of carbopol 934P and hydroxypropyl methylcellulose (HPMC K4M) polymers were used and evaluated by rheological and in vitro drug release studies. The optimized formulation (F4), containing carbopol 934P 0.2% (w/v) and HPMC K4M 0.2% (w/v), was evaluated for clarity, pH, gelling capacity, drug content, rheological properties, in vitro drug release pattern, ocular irritation test and antimicrobial efficacy. Finally, owing to the improved antimicrobial efficacy and increased residence time, AZM:SBE-β-CD in situ gel was found to be a promising formulation for the efficient treatment of bacterial ocular disease.

Formulation and Evaluation of Tacrolimus Transdermal Gel

The present investigation is concerned with formulation and evaluation of Transdermal gels of Tacrolimus, anti-psoriasis drug, to circumvent the first pass effect and to improve its bioavailability with reduction in dosing frequency and dose related side effects. Twelve formulations were developed with varying concentrations of polymers like Carbopol 934P, HPMCK4M and Sodium CMC. The gels were tested for clarity, Homogeneity, Spreadability, Extrudability, Viscosity, surface pH, drug Content uniformity, in-vitro drug diffusion study and ex-vivo permeation study using rat abdominal skin. FTIR studies showed no evidence on interactions between drug, polymers and excipients. The best in-vitro drug release profile was achieved with the formulation F4 containing 0.5 mg of exhibited 6 hr drug release i.e. 98.68 % with desired therapeutic concentration which contains the drug and Carbopol 934p in the ratio of 1:2. The surface pH, drug content and viscosity of the formulation F4 was found to be 6.27, 101.3% and 3, 10,000cps respectively. The drug permeation from formulation F4 was slow and steady and 0.89gm of tacrolimus could permeate through the rat abdominal skin membrane with a flux of 0.071 gm hr-1 cm-2. The in-vitro release kinetics studies reveal that all formulations fit well with zero order kinetics followed by non-Fickian diffusion mechanism. Keywords: Transdermal gel, Viscosity, In-vitro drug release, In-vitro drug release kinetics study, Ex-vivo permeation study