FORMULATION AND EVALUATION OF OPHTHALMIC GEL BASED ON DRUG-POLYMER-POLYMER TERNARY INTERACTION

 Objective: The objective was to enhance the amount of active substance reaching the target tissue or exerting a local effect in the cul-de-sac, theapproach we use is the application of in-situ gelling systems or phase transition systems, which are instilled in a liquid form and shift to a gel or solidphase in the cul-de-sac. The present study will focus on the development of formulation of ophthalmic gels. The polymer physicochemical propertieswere studied for the improvement in gel characteristics.Methods: The formulations were varied by the amount of the anionic and cationic polymer concentration. The 10 and 20-fold excess anionic polymerwere used. The 10 and 20-fold excess anionic polymer were used. Further cationic polymers were utilized to see any ternary interaction betweendrug and polymers.Results: From the present study it could be shown that most of the formulations were isotropic and could be clearly separated from the anisotropicones which were situated at the cationic side of the phase diagram only as well as at 10% polyvinyl alcohol. Furthermore, excess 20HA, 10PAA, and20PAA as well as HCS (HCS/20PAA) contributes to improve drug release control.Conclusion: The above formulation of were found to be quite stable and useful in the novel format of sol-gel transformations. Further, the physicalcharacteristics gels show better tolerability with anionic and cationic polymer.Keywords: Cationic, Anionic, Poloxamer, Sol-gel

ESTIMATION OF THE DRUG-DRUG AND DRUG-POLYMER OPHTHALMIC COMPLEX AT STOICHIOMETRY BY TERNARY PHASE BEHAVIOUR

Objective: The study focus on the drug-drug and drug-polymer interaction and their estimation at stoichiometry when such systems were formed. In this discovery we tried to make use of the latest research and novel concepts to explore the drug-polymer-polymer Ionic ternary InteractionMethods: Partial ternary phase diagrams were constructed and the stoichiometry of the ciprofloxacin/anionic polymer interaction was assessed in distilled water by means of dialysis equilibrium. The polymers were completely hydrated in distilled water by gentle stirring at room temperature and studied for viscosity and turbidimetric measurements.Results: Comparing the partial ternary phase diagrams of the different anionic to each other. PAA exhibited the largest gel area even with low polymer content. The anionic polymers HA and PAA showed good capability to interact with the drug giving soluble drug/polymer complexes; moreover they were able to form polymer/polymer complexes with Poloxamer and HCS, with a stoichiometry depending on the polymers involved.Conclusion: From the results of the present study, it can be concluded that formulations were made isotonic and favours corneal permeation of both the drug. Ocular Irritancy denotes formulations were quite stable & useful in novel format of sol-gel transformations.Â

DEVELOPMENT OF THERMOSENSITIVE GEL OF FLUCONAZOLE FOR VAGINAL CANDIDIASIS

Objective: The aim of the present study was to develop in-situ gelling formulations of Fluconazole (FCZ) using thermosensitive polymer for treatment of vaginal Candidiasis.Methods: In-situ gelling formulations of FCZ (1 % w/w) were prepared with different concentrations of Poloxamer 407 (P 407, 15-20% w/w) using the cold dispersion method. Similarly,  formulations were also prepared by adding mucoadhesive polymers like hydroxyethyl cellulose, Polycarbophil, Carbopol 974 and Hydroxypropyl methylcellulose E 50 LV (0.4 % w/w) to the P 407 formulations. These formulations were evaluated for appearance, clarity, pH, gelling ability, gelling time, gelling temperature, viscosity (in sol and gel forms), spreading time, ex-vivo mucoadhesion, in-vitro dissolution, morphological characteristics by SEM and in-vitro antifungal efficacy against Candida albicance. In-vivo vaginal irritation of developed formulation was assessed in New Zealand female rabbits. Results: In-situ gelling formulation of FCZ, prepared using 18 % w/w P407 and 0.4 % hydroxyethyl cellulose, was optimized since this formulation was found to be clear, transparent, forming a quick and stable gel with shear thinning behaviour and excellent mucoadhesion. The developed formulation released 74.21% of FCZ after 8 h of dissolution in 5.2 pH citrate buffer. In-vitro antifungal activity against Candida albicance showed the stronger antifungal activity of formulation as compared to a marketed formulation. In-vivo vaginal irritation study in rabbits demonstrated no significant irritation after 10 d of exposure to the formulation. Conclusion: The study demonstrated that in-situ gelling formulation of FCZ prepared using thermosensitive polymer had improved activity against Candida albicance and would be efficacious for the treatment of vaginal Candidiasis

EVALUATION OF GUM SANDARAC AS A NOVEL RELEASE CONTROLLING POLYMER FOR SUSTAINED RELEASE MATRIX PELLETS

Sustained release, prolonged action, extended action are the terms used to identify drug delivery system that are designed to achieve prolong therapeutic effect by continuously releasing medication over an extended period of time after administration of a single dose. Matrix systems, because of their ease of manufacture, their flexibility to obtain a desirable drug release profile, cost effectiveness, and broad regulatory acceptance are preferred for formulating these dosage forms. Polymers are the most important part in any type of release modified formulations. Predominantly hydrophobic materials are widely used to fabricate the matrix systems. Various materials are being investigated as polymers as there is scarcity of good polymeric materials to be used in pharmaceutical products. The present study was aimed at evaluating novel natural material gum sandarac, a resin obtained by incision from the stem of Callitris quadrivalvis, Ventenat (N.O. Coniferae) Pinaceae as a hydrophobic matrixing material for developing coated pellets for sustained release of drug and comparing it with well known ethyl cellulose as hydrophobic polymeric material

Kaempferol-Phospholipid Complex: Formulation, and Evaluation of Improved Solubility, In Vivo Bioavailability, and Antioxidant Potential of Kaempferol

The current work describes the formulation and evaluation of a phospholipid complex of kaempferol toenhance the latter’s aqueous solubility, in vitro dissolution rate, in vivo antioxidant and hepatoprotectiveactivities, and oral bioavailability. The kaempferol-phospholipid complex was synthesized using a freeze-drying method with the formulation being optimized using a full factorial design (32) approach. The resultsinclude the validation of the mathematical model in order to ascertain the role of specific formulation andprocess variables that contribute favorably to the formulation’s development. The final product wascharacterized and confirmed by Differential Scanning Calorimetry (DSC), Fourier Transform InfraredSpectroscopy (FTIR), Proton Nuclear Magnetic Resonance Spectroscopy (1H-NMR), and Powder X-rayDiffraction (PXRD) analysis. The aqueous solubility and the in vitro dissolution rate were enhanced comparedto that of pure kaempferol. The in vivo antioxidant properties of the kaempferol-phospholipid complex wereevaluated by measuring its impact on carbon tetrachloride (CCl4)-intoxicated rats. The optimizedphospholipid complex improved the liver function test parameters to a significant level by restoration of allelevated liver marker enzymes in CCl4-intoxicated rats. The complex also enhanced the in vivo antioxidantpotential by increasing levels of GSH (reduced glutathione), SOD (superoxide dismutase), catalase anddecreasing lipid peroxidation, compared to that of pure kaempferol. The final optimized phospholipidcomplex also demonstrated a significant improvement in oral bioavailability demonstrated by improvementsto key pharmacokinetic parameters, compared to that of pure kaempferol

Drug-Phospholipid Complex-loaded Matrix Film Formulation for the Enhanced Transdermal Delivery of Quercetin

A novel quercetin-phospholipid-complex(QPLC)-loaded matrix film for improved transdermal delivery of quercetin was developed. The QPLC formulation, prepared using a solvent-evaporation method, was optimized using a central-composite design. The optimized QPLC formulation was characterized by particle size and zeta potential analysis, thermal analysis, Fourier transform infrared spectroscopy (FTIR), and proton nuclear magnetic resonance spectroscopy (1H-NMR). QPLC formulation was functionally evaluated for solubility and in vitro dissolution of quercetin. Matrix films of pure quercetin (Q-MF)or QPLC QPLC-MF) were prepared using a solvent casting method. The prepared Q-MF and QPLC-MF were characterized for weight uniformity, folding endurance, moisture content, and moisture uptake. The films were also functionally characterized for in vitro diffusion of quercetin through a dialysis membrane and ex vivo permeability of quercetin across rat skin. Finally, the anti-inflammatory activity of the films was evaluated on carrageenan-induced paw edema in Wistar albino rats. The experimental design identified the optimal formulation and process variables for the preparation of QPLC. The validation of the obtained model using these values confirmed the suitability and robustness of the model. The physical-chemical characterization of the prepared QPLC supported the formation of a stable complex. The solubility analysis of QPLC showed a 22-fold increase in quercetin aqueous solubility, compared to pure quercetin. The dissolution results exhibited a significantly higher rate and extent of quercetin dissolution from QPLC compared to that of pure quercetin. The permeability of quercetin from Q-MF and QPLC-MF across rat skin mirrored those obtained from the dissolution studies. Topical application of QPLC-MF exhibited a significant (p\u3c0.05) inhibition of carrageenan-induced paw edema in rats compared to that of Q-MF. This study provides a promising combination approach, i.e., phospholipid-based complexation and transdermal film formulation for improved transdermal delivery of quercetin and similar pharmacologically active phytoconstituents

Glucosamine HCl-based solid dispersions to enhance the biopharmaceutical properties of acyclovir

The objective of the work presented here was to assess the feasibility of using glucosamine HCl as a solid-dispersion (SD) carrier to enhance the biopharmaceutical properties of a BCS class III/IV drug, acyclovir (ACV). The solid-dispersions of acyclovir and glucosamine HCl were prepared by an ethanol-based solvent evaporation method. The prepared formulations characterized by photomicroscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transforms infrared spectrophotometry (FTIR), powder x-ray diffractometry (PXRD) and drug content analysis. The functional characterization of ACV-SD was performed by aqueous solubility evaluation, dissolution studies, fasted versus fed state dissolution comparison, ex vivo permeability, and stability studies. Photomicroscopy and SEM analysis showed different surface morphologies for pure ACV, glucosamine HCl and ACV-SD. The physical-chemical characterization studies supported the formation of ACV-SD. A 12-fold enhancement in the aqueous solubility of ACV was observed in the prepared solid dispersions, compared to pure ACV. Results from in vitro dissolution demonstrated a significant increase in the rate and extent of ACV dissolution from the prepared ACV-SD formulations, compared to pure ACV. The rate and extent of ACV permeability across everted rat intestinal membrane were also found to be significantly increased in the ACV-SD formulations. Under fed conditions, the rate and extent of the in vitro dissolution of ACV from the formulation was appreciably greater compared to fasted conditions. Overall, the results from the study suggest the feasibility of utilizing glucosamine HCl as a solid dispersion carrier/excipient for enhancement of biopharmaceutical properties of acyclovir, and similar drugs with low solubility/permeability characteristics

INVESTIGATION OF EFFECT OF PHOSPHOLIPIDS ON PHYSICAL AND FUNCTIONAL CHARACTERIZATION OF PACLITAXEL LIPOSOMES

Objective: Aim of the present investigation was to determine the effect of various synthetic grades of phospholipids on paclitaxel liposomes (PTL).Methods: The PTL formulations using various grades of phospholipids were prepared by film hydration method. The prepared PTL formulations were physicochemically characterized by entrapment efficiency (EE, %w/w), vesicular size and particle size distribution. These formulations were also characterized for function parameters such as in vitro release and hemolytic toxicity assay.Results: The synthetic grades of phospholipids significantly influenced PTL formulations. The stoichiometric ratio (1:1) between CH and various synthetic phospholipids was found to be optimized one, from rest of the ratios. The characterization confirmed the formation of PTL. The EE was observed to be high (86.67%) as increasing the ratios between CH and phospholipids but then declined suddenly as further increasing the ratio. The best liposomal formulations showed that the spherical shape was found to be within size ranging from<10 µm, with a higher rate and extent of the release, ~86.22% of paclitaxel from PTL formulation. The results of the hemolytic toxicity study demonstrated that PTL formulations with a ratio (1:1) exhibited a significantly lower hemolytic toxicity (2.70%), compared to all formulations.Conclusion: The result revealed the excellent effect of phospholipids on paclitaxel liposomes. The paclitaxel liposomes prepared with CH: PL90G ratio (1:1) was found to be optimized one. The entrapment efficiency, particle size distribution, in vitro release and hemolytic activity with this ratio shown to be excellent as compared to other ratios

An Unusual Presentation of “Two-Thirds Tumor” in the Mandible – A Diagnostic Quandary with a Review of the Literature

An adenomatoid odontogenic tumor (AOT) is an uncommon benign tumor of the oral cavity commonly found in the maxillary anterior region and is associated with impacted canines in young females. It rarely occurs in the mandibular region with no impacted or missing teeth. A 21-year-old female reported to the clinic with swelling on the right side of the face for the past six months with no history of pain. Radiographic features such as unilocular radiolucency with thinning of the cortical borders and considerable buccal cortical expansion, as well as some evidence of radiopaque specks were noted. Histopathological examination revealed cells with hyperchromatic nuclei, rosette-like structures with focal areas of calcified mass, and concentric rings resembling Liesegang rings, suggestive of AOT. The tumor was treated surgically by enucleation and cauterization. Although follicular type is a common variant, the tumor presented in this case was of extrafollicular type noted in the mandibular canine and premolar regions of a young female patient with no related impacted tooth

Formulation and Characterization of the Improved Solubility, In Vivo Bioavailability and Antioxidant Activity of Apigenin-Phospholipid Complex (APLC)

In the present study a phospholipid based complex of apigenin (APLC) was prepared with a goal of improving its aqueous solubility, dissolution, in vivobioavailability, and antioxidant activity