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Topical therapy is desirable in treatment of nail diseases like onychomycosis (fungal infection of nail) and psoriasis. The topical treatment avoids the adverse effects associated with systemic therapy, thereby enhancing the patient compliance and reducing the treatment cost. However the effectiveness of the topical therapies has been limited due to the poor permeability of the nail plate to topically applied therapeutic agents. Research over the past one decade has been focused on improving the transungual permeability by means of chemical treatment, penetration enhancers, mechanical and physical methods. The present review is an attempt to discuss the different physical and chemical methods employed to increase the permeability of the nail plate. Minimally invasive electrically mediated techniques such as iontophoresis have gained success in facilitating the transungual delivery of actives. In addition drug transport across the nail plate has been improved by filing the dorsal surface of the nail plate prior to application of topical formulation. But attempts to improve the trans-nail permeation using transdermal chemical enhancers have failed so far. Attempts are on to search suitable physical enhancement techniques and chemical transungual enhancers in view to maximize the drug delivery across the nail plate.

A 32 factorial design was employed to produce glipizide lipospheres by the emulsification phase separation technique using paraffin wax and stearic acid as retardants. The effect of critical formulation variables, namely levels of paraffin wax (X1) and proportion of stearic acid in the wax (X2) on geometric mean diameter (dg), percent encapsulation efficiency (% EE), release at the end of 12 h (rel12) and time taken for 50% of drug release (t50), were evaluated using the F-test. Mathematical models containing only the significant terms were generated for each response parameter using the multiple linear regression analysis (MLRA) and analysis of variance (ANOVA). Both formulation variables studied exerted a significant influence (p < 0.05) on the response parameters. Numerical optimization using the desirability approach was employed to develop an optimized formulation by setting constraints on the dependent and independent variables. The experimental values of dg, % EE, rel12 and t50 values for the optimized formulation were found to be 57.54 +/- 1.38 mum, 86.28 +/- 1.32%, 77.23 +/- 2.78% and 5.60 +/- 0.32 h, respectively, which were in close agreement with those predicted by the mathematical models. The drug release from lipospheres followed first-order kinetics and was characterized by the Higuchi diffusion model. The optimized liposphere formulation developed was found to produce sustained anti-diabetic activity following oral administration in rats.

The main objective of this novel study was to develop chlorpheniramine maleate orally disintegrating films (ODF) using hot-melt extrusion technology and evaluate the characteristics of the formulation using in vitro and in vivo methods. Modified starch with glycerol was used as a polymer matrix for melt extrusion. Sweetening and saliva-simulating agents were incorporated to improve palatability and lower the disintegration time of film formulations. A standard screw configuration was applied, and the last zone of the barrel was opened to discharge water vapors, which helped to manufacture non-sticky, clear, and uniform films. The film formulations demonstrated rapid disintegration times (6–11 s) and more than 95% dissolution in 5 min. In addition, the films had characteristic mechanical properties that were helpful in handling and storage. An animal model was employed to determine the taste masking of melt-extruded films. The lead film formulation was subjected to a human panel for evaluation of extent of taste masking and disintegration.

The objective of this study was to develop caffeine citrate orally disintegrating tablet (ODT) formulations utilizing hot-melt extrusion technology and evaluate the ability of the formulation composition to mask the unpleasant bitter taste of the drug using in vitro and in vivo methods. Ethylcellulose, along with a suitable plasticizer, was used as a polymeric carrier. Pore forming agents were incorporated into the extruded matrix to enhance drug release. A modified screw configuration was applied to improve the extrusion processability and to preserve the crystallinity of the API. The milled extrudates were subjected to dissolution testing in an artificial salivary fluid and investigations using e-tongue, to assess the extent of masking of bitter taste of the API. There was an insignificant amount of drug released from the formulation in the salivary medium while over 80% of drug released within 30 min in 0.1 N HCl. ODTs were also developed with the extrudate mixed with mannitol and crospovidone. The quality properties such as friability and disintegration time of the ODTs met the USP specifications. The lead extrudate formulations and the ODTs prepared using this formulation were subjected to human gustatory evaluation. The formulations were found to mask the unpleasant taste of caffeine citrate significantly.

A 32 factorial design was employed to produce controlled release solid dispersions of diclofenac sodium in Eudragit RS and RL by coevaporation of their ethanol solution in a flash evaporator. The effect of critical formulation variables namely total polymer pay loads and levels of Eudragit RL on percent drug incorporation (% DI), drug release at the end of 12 hours (Rel12) and drug release at the end of 3 hours (Rel3) were analyzed using response surface methodology. The parameters were evaluated using the F test and mathematical models containing only the significant terms were generated for each parameter using multiple linear regression analysis and analysis of variance. Both the formulation variables studied exerted a significant influence (p < 0.05) on the drug release whereas the total polymer levels emerged as a lone factor significantly influencing the percent drug incorporation. Numerical optimization technique employing desirability approach was used to develop a new formulation by setting constraints on the dependent and independent variables. The experimental values of % DI, Rel12 and Rel3 for the optimized batch were found to be 95.22 ± 1.13%, 74.52 ± 3.16% and 29.37 ± 1.26% respectively which were in close agreement with those predicted by the mathematical models. The Fourier transform infrared spectroscopy, Differential scanning calorimetry and Powder x-ray diffractometry confirmed that the drug was reduced to molecular or microcrystalline form in the hydrophobic polymeric matrices, which could be responsible for the controlled drug release from the solid dispersions. The drug release from the solid dispersions followed first order rate kinetics and was characterized by Higuchian diffusion model.

The purpose of the current study was to investigate the plausibility of delivery of ziconotide to the cerebrospinal fluid (CSF) via intranasal administration. Ziconotide was administered either in the form of solution or Kolliphor P 407 gels (KP 407) intranasally in Sprague-Dawley rats. The effect of incorporation of chitosan in the formulation was also investigated. Time course of drug in the CSF was investigated by collecting CSF from cisterna magna. Pharmacokinetics of ziconotide in CSF following intrathecal and intravenous (i.v) administration of ziconotide was investigated. Upon intrathecal administration the elimination rate constant of ziconotide in CSF was found to be 1.01 ± 0.34 h−1. The Cmax and Tmax of ziconotide in CSF following intravenous administration were found to be 37.78 ± 6.8 ng/mL and ~2 h respectively. The time required to attain maximum concentration (Tmax) in CSF was less upon intranasal administration (15 min) compared to i.v administration (120 min). Presence of chitosan enhanced the overall bioavailability of ziconotide from intranasal solution and gel formulations. The elimination rate constant of ziconotide in CSF following intranasal and intravenous administration of ziconotide solution was found to be 0.54 ± 0.08 h−1 and 0.42 ± 0.10 h−1 respectively. Whereas, intranasal administration of ziconotide in the form of in situ forming gel lowered the elimination rate significantly. These results suggest that intranasal administration could be a potential noninvasive and patient compliant method of delivering ziconotide to CSF to treat chronic pain.

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