Marina Koland

Formulation and evaluation of fast dissolving films of levocitirizine di hydrochloride

Introduction: Levocetirizine dihydrochloride is an orally active, third-generation non-sedative antihistamine used in the symptomatic relief of seasonal and perennial allergic rhinitis. The present work aimed at preparing quick release films of levocetirizine with the purpose of developing a dosage form for a very quick onset of action, which is beneficial in managing severe conditions of allergies, aiding in the enhancement of bioavailability, and is very convenient for administration, without the problem of swallowing and using water. Materials and Methods: The films of levocetirizine dihydrochloride were prepared by using polymers such as hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA), as either single polymer or in combination of two, by a solvent casting method. They were evaluated for physical characteristics such as uniformity of weight, thickness, folding endurance, drug content uniformity, surface pH, percentage elongation, and tensile strength, and gave satisfactory results. The formulations were subjected to disintegration, in vitro drug release tests, and in vivo studies on rats. Results: A marked increase in the dissolution rate was exhibited by fast-dissolving films of levocetirizine dihydrochloride containing HPMC as a polymer, when compared to conventional tablets. The haloperidol-induced catalepsy, milk-induced leukocytosis, and nasal provocation in vivo studies in rats proved that the fast-dissolving films of levocetirizine dihydrochloride produced a faster onset of action compared to the conventional tablets. Conclusions: Fast dissolving films of levocetirizine dihydrochloride can be considered suitable for clinical use in the treatment of allergic rhinitis and other conditions of allergies, where a quicker onset of action for a dosage form is desirable along with the convenience of administration.

Investigation of nano lipid vesicles of methotrexate for anti-rheumatoid activity

Background The purpose of this study was to formulate and evaluate nano lipid vesicles of methotrexate (MTX) for its anti-rheumatoid activity. Methods In this study the principle of both active as well as passive targeting using MTX-loaded stealth liposomes as per the magic gun approach was followed. Stealth liposomes of MTX were prepared by thin-film hydration method using a PEGylated phospholipid-like DSPE-MPEG 2000. Similarly, conventional liposomes were prepared using phospholipids like DPPC and DSPC. Conventional liposomes were coated with a hydrophilic biocompatible polymer like chitosan. They were investigated for their physical properties and in vitro release profile. Further, in vivo screening of the formulations for their anti-rheumatoid efficacy was carried out in rats. Rheumatoid arthritis was induced in male Wistar-Lewis rats using complete Freund’s adjuvant (1 mg/mL Mycobacterium tuberculosis, heat killed in mineral oil). Results It was found that chitosan coating of the conventional liposomes increased the physical stability of the liposomal suspension as well as its entrapment efficiency. The size of the unsonicated lipid vesicles was found to be in the range of 8–10 μm, and the sonicated lipid vesicles in the range of 210–260 nm, with good polydispersity index. Further, chitosan-coated conventional liposomes and the PEGylated liposomes released the drug for a prolonged period of time, compared to the uncoated conventional liposomes. It was found that there was a significant reduction in edema volume in the rat group administered with the test stealth liposomal formulations and chitosan-coated conventional liposomes (PEGylated and chitosan-coated conventional) compared to that of the control and standard (administered with free MTX) group of rats. PEGylated liposomes showed almost equal efficacy as that of the chitosan-coated conventional liposomes. Conclusion Lipid nano vesicles of MTX can be administered by intravenous route, whereby the drug selectively reaches the target site with reduced toxicity to other organs.

In vitro and in vivo evaluation of chitosan buccal films of ondansetron hydrochloride

Buccal films of ondanstron hydrochloride were fabricated from mucoadhesive polymer, chitosan, and polyvinyl pyrrolidone (PVP K30) for the purpose of prolonging drug release and improving its bioavailability. All fabricated film formulations prepared were smooth and translucent, with good flexibility. The weight and thickness of all the formulations were found to be uniform. Drug content in the films ranged from 98 – 99%, indicating favorable drug loading and uniformity. The inclusion of PVP K30, a hydrophilic polymer, significantly reduced the bioadhesive strength and in vitro mucoadhesion time of the films, although the degree of swelling increased. In vitro drug release studies in simulated saliva showed a prolonged release of over five to six hours for all formulations, except C4, with 99.98% release in 1.5 hours. Kinetic analysis of the release data indicated that the best fit model with the highest correlation coefficient for all formulations was the Peppas model. In vivo studies, on selected films in rabbits, were conducted, to determine the pharmacokinetic parameters such as Cmax, Tmax, and AUC0-∞, using model-independent methods with nonlinear least-squares regression analysis. The AUC and values of Cmax of ondansetron hydrochloride were found to be significantly greater (P < 0.005) than the selected films C2 and C3, as compared to those from the oral solution, thereby confirming improved bioavailability via the buccal route. The Tmax values were also significantly greater (P < 0.005), indicating the slower release of the drug from buccal films, thereby, providing prolonged effects. Good in vitro-in vivo correlation was observed with R2 values exceeding 0.98, when the percentage of drug released was correlated with the percentage of drug absorbed.

Investigation of the ex vivo and in vivo iontophoretic delivery of aceclofenac from topical gels in Albino rats

Introduction: Iontophoresis was used to enhance the delivery of aceclofenac (ACF) from topical gels formulated with various polymers for the purpose of relieving pain and inflammation. Materials and Methods Gels were formulated from hydroxypropyl methyl cellulose (HPMC), carbopol 934P, and sodium carboxymethyl cellulose (NaCMC). The formulations were evaluated for cathodal iontophoretic delivery of ACF through excised rat abdominal skin at three levels of current density of 0.5, 0.6 and 0.7 mA/cm2. The in vivo effectiveness of the drug delivered passively as well as under the influence of iontophoresis at pH 7.4 at a current density of 0.5 mA/cm2 was also investigated using male Albino rats with carrageenan induced paw edema. Results and Discussion: In the ex vivo studies, though it was clear that iontophoresis significantly increased drug permeation through the excised skin from all formulations; the percentage drug permeated from HPMC gels was superior to that from carbopol 934P or NaCMC gels but increased with an increase in the current density only for the former. The steady state flux, permeability coefficient, enhancement factor were significantly greater from HPMC gels than from the gels of the ionic polymers due to the interference of competitive ions. With iontophoresis, the carrageenan induced paw edema was significantly reduced by 61.53% (P < 0.01) for HPMC gels as compared to the control although passive permeation without iontophoresis showed a 54.6% reduction (P < 0.05) at the end of 4 h. Conclusion: The results of the study indicate that ACF could be administered topically by using iontophoresis from a suitably formulated gel for effective control of pain and inflammation.