Mohammed Aqil

Nanoemulsions as vehicles for transdermal delivery of aceclofenac

The aim of the present study was to investigate the potential of a nanoemulsion formulation for transdermal delivery of aceclofenac. Various oil-in-water nanoemulsions were prepared by the spontaneous emulsification method. The nanoemulsion area was identified by constructing pseudoternary phase diagrams. The prepared nanoemulsions were subjected to different thermodynamic stability tests. The nanoemulsion formulations that passed thermodynamic stability tests were characterized for viscosity, droplet size, transmission electron microscopy, and refractive index. Transdermal permeation of aceclofenac through rat abdominal skin was determined by Franz diffusion cell. The in vitro skin permeation profile of optimized formulations was compared with that of aceclofenac conventional gel and nanoemulsion gel. A significant increase in permeability parameters such as steady-state flux (Jss), permeability coefficient (Kp), and enhancement ratio (Er) was observed in optimized nanoemulsion formulation F1, which consisted of 2% wt/wt of aceclofenac, 10% wt/wt of Labrafil®, 5% wt/wt of Triacetin®, 35.33% wt/wt of Tween 80®, 17.66% wt/wt of Transcutol P®, and 32% wt/wt of distilled water. The anti-inflammatory effects of formulation F1 showed a significant increase (P<.05) in percent inhibition value after 24 hours when compared with aceclofenac conventional gel and nanoemulsion gel on carrageenan-induced paw edema in rats. These results suggested that nanoemulsions are potential vehicles for improved transdermal delivery of aceclofenac.

Sparfloxacin-loaded PLGA nanoparticles for sustained ocular drug delivery

UNLABELLED Poor ocular bioavailability of drugs (<1%) from conventional eye drops (ie, solution, suspension, and ointments) is mainly due to the physiologic barriers of the eye. In general, ocular efficacy is closely related to ocular drug bioavailability, which may be enhanced by increasing corneal drug penetration and prolonging precorneal drug residence time. In our current work, we develop and evaluate a new colloidal system, that is, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles for sparfloxacin ophthalmic delivery, to improve precorneal residence time and ocular penetration. Nanoparticles were prepared by nanoprecipitation technique and characterized for various properties such as particle size, zeta potential, in vitro drug release, statistical model fitting, stability, and so forth. Microbiological assay was carried out against Pseudomonas aeruginosa using the cup-plate method. Precorneal residence time was studied in albino rabbits by gamma scintigraphy after radiolabeling of sparfloxacin by Tc-99m. Ocular tolerance of the developed nanosuspension was also studied by the Hen Egg Test-Chorioallantoic Membrane (HET-CAM) method. The developed nanosuspension showed a mean particle size in the range of 180 to 190 nm, suitable for ophthalmic application with zeta potential of -22 mV. In vitro release from the developed nanosuspension showed an extended release profile of sparfloxacin according to the Peppas model. Acquired gamma camera images showed good retention over the entire precorneal area for the developed nanosuspension compared with that of a marketed formulation. The marketed drug formulation cleared very rapidly from the corneal region and reached the systemic circulation through the nasolacrimal drainage system, as significant radioactivity was recorded in kidney and bladder after 6 hours of ocular administration, whereas the developed nanosuspension cleared at a very slow rate (P < .05) and remained at the corneal surface for longer duration, as no radioactivity was observed in the systemic circulation. HET-CAM assay with 0 score in 8 hours indicates the nonirritant property of the developed nanosuspension. The developed lyophilized nanosuspension was found to be stable for a longer duration of time than the conventional marketed formulation with a good shelf life. FROM THE CLINICAL EDITOR Poor ocular bioavailability of drugs (<1%) from conventional eye drops is mainly due to the eye physiological barriers. In this study, a new colloidal system, PLGA nanoparticle for sparfloxacin ophthalmic delivery was demonstrated to improve precorneal residence time and ocular penetration. The developed lyophilized nanosuspension was found to be stable for longer duration of time than conventional marketed formulations.

Formulation and optimization of nanotransfersomes using experimental design technique for accentuated transdermal delivery of valsartan

UNLABELLED The purpose of this work was to develop and statistically optimize nanotransfersomes for enhanced transdermal of valsartan vis-à-vis traditional liposomes. Nanotransfersomes bearing valsartan were prepared by conventional rotary evaporation method and characterized for various parameters including entrapment efficiency, vesicles shape, size, size distribution, and skin permeation. In vivo antihypertensive activity conducted on Wistar rats was also taken as a measure of performance of nanotransfersomes and liposomes. Nanotransfersomes proved significantly superior in terms of amount of drug permeated in the skin, with an enhancement ratio of 33.97 ± 1.25 when compared to rigid liposomes. This was further confirmed through a confocal laser scanning microscopy study. Nanotransfersomes showed better antihypertensive activity in comparison to liposomes by virtue of better permeation through Wistar rat skin. Finally, it could be concluded that the nanotransfersomes accentuates the transdermal flux of valsartan and could be used as a carrier for effective transdermal delivery of valsartan. FROM THE CLINICAL EDITOR In this paper, the authors discuss the development and optimization of nanotransfersomes for enhanced transdermal of valsartan and demonstrate accentuated transdermal compared to standard preparations.

The emerging role of P-glycoprotein inhibitors in drug delivery: a patent review

Introduction: The ATP-binding cassette superfamily contains membrane transporter proteins that transport a wide range of diverse compounds across cellular membranes. The P-glycoprotein (P-gp) is an important member of this family and a multi-specific drug efflux transporter that plays a significant role in governing the bioavailability of many clinically active drugs. The inhibition of this efflux transporter by various P-gp inhibitors forms a distinctive approach in improving bioavailability and conquering drug resistance. Most P-gp inhibitors exhibit limitations associated with their safety and unwanted pharmacokinetic interactions, thereby restraining their clinical applicability. Areas covered: This review explores the investigations on the feasibility and applicability of various classes of P-gp inhibitors as described in recent patents for enhanced drug delivery. Expert opinion: Several candidates presently under development look promising as P-gp inhibitors, e.g., tariquidar and elacridar. Pharmaceutical excipients currently constitute the most promising class of P-gp inhibitors and are considered safe and pharmaceutically acceptable for use in formulations. In addition, lipid-based excipients and thiolated polymers play an active role in affecting P-gp-mediated transport not only by altering the membrane fluidity or ATPase activity but by down regulating P-gp expression. An additional overture such as the prodrug derivatization of P-gp substrates is a feasible approach to bypass P-gp-mediated efflux.

Chemical penetration enhancers: a patent review

Background: Ever since transdermal drug delivery came into existence, it has offered great promises, although most of them are yet to be fulfilled owing to some intrinsic restrictions of the transdermal route. On the positive side, transdermal drug delivery systems present advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. The greatest hindrance in the percutaneous delivery is the obstruction property of the stratum corneum, the outermost layer of the skin, in addition to usual problems such as skin binding, skin metabolism, cutaneous toxicity and prolonged lag times. Objective: This paper reviews investigations on the feasibility and application of penetration enhancers as described in recent patents, which help in the selection of a suitable sorption promoter(s) for enhanced delivery of medicaments through the skin. Method: The patents granted under various categories of penetration enhancers have been discussed including fatty acids, terpenes, fatty alcohol, pyrrolidone, sulfoxides, laurocapram, surface active agents, amides, amines, lecithin, polyols, quaternary ammonium compounds, silicones, alkanoates and so on. Conclusion: Scores of promising chemicals have been harnessed for their skin permeation promoting capacity as mentioned earlier. In future, many more chemicals and putative enhancers are likely be documented and patented.

Role of novel terpenes in transcutaneous permeation of valsartan: effectiveness and mechanism of action

Context: The greatest obstacle for transdermal delivery is the barrier property of the stratum corneum. Many approaches have been employed to breach the skin barrier; the most widely used one is that of chemical penetration enhancers. Of the penetration enhancers, terpenes are arguably the most highly advanced and proven category. Objective: The aim of this investigation was to study effectiveness and mechanism of seven novel terpenes, namely iso-eucalyptol, β-citronellene, valencene, rose oxide, safranal, lavandulol acetate, and prenol, as potential penetration enhancers for improved skin permeation of valsartan through rat skin and human cadaver skin (HCS) with reference to established terpene eucalyptol. Methods: Skin permeation studies were carried out using Automated Transdermal Diffusion Cell Sampling System (SFDC 6, LOGAN Instruments Corp., NJ) on rat skin and HCS. The mechanism of skin permeation enhancement of valsartan by terpenes treatment was evaluated by Fourier transform infrared spectroscopy (FT-IR) analysis, differential scanning calorimetry (DSC) thermogram, and histopathological examination. Results and discussion: Among all study enhancers, iso-eucalyptol produced the maximum enhancement via rat skin [enhancement ratio (ER) = 7.4] and HCS (ER = 3.60) over control. FT-IR spectra and DSC thermogram of skin treated with aforesaid terpenes indicated that permeation occurred due to the disruption of lipid bilayers. No apparent skin irritation (erythema, edema) was observed on treatment with terpenes except β-citronellene, safranal, lavandulol acetate, and prenol, which caused mild irritation. Conclusion: It is concluded that the iso-eucalyptol can be successfully used as safe and potential penetration enhancer for enhancement of skin permeation of lipophilic drug such as valsartan.

Interactions between novel terpenes and main components of rat and human skin: mechanistic view for transdermal delivery of propranolol hydrochloride.

The purpose of this study was to investigate the effectiveness and mechanism(s) of percutaneous absorption of propranolol hydrochloride (PHCL) across rat and human cadaver skin using seven novel terpenes with reference to marker terpene 1,8-cineole. In-vitro skin permeation studies were carried out via rat and human skin models. The mechanism of skin permeation of PHCL by terpenes was evaluated by FTIR, DSC, activation energy measurement and histopathological examination. Amongst the new terpenes, 1,4-cineole was found to be most effective enhancer for diffusion of PHCL through rat skin (ER=3.07) and human cadaver skin (ER=2.42) as compared to control. FTIR spectra and DSC thermogram of skin treated with aforesaid terpenes indicated that permeation occurred due to the disruption of lipid bilayers. No apparent skin irritation (erythema, edema) was observed on treatment of skin with terpenes, the irritation was higher with the β-citronellene and rose oxide. It was concluded that 1,4-cineole can be successfully used as potential permeation enhancer for PHCL. It enhanced the absorption of hydrophilic drug by extraction and disruption of lipid bilayers and keratin denaturation of stratum corneum.

Transdermal delivery of valsartan: I. Effect of various terpenes.

The objective of the present study was to investigate the effect of various terpenes, including a diterpene, forskolin (FSK; a putative penetration enhancer), on skin permeation of valsartan. Permeation studies were carried out with Automated Transdermal Diffusion Cells Sampling System (SFDC 6, LOGAN Instruments Corp., NJ, USA) through rat skin and human cadaver skin (HCS) using ethanol: IPB (pH 7.4) (40:60) as vehicle. The efficacy of the study terpenes for permeation of valsartan across rat skin and human cadaver skin was found in the order of cineole > d-limonene > l-menthol > linalool > FSK and cineole > d-limonene > linalool > l-menthol > FSK, respectively. No apparent skin irritation (erythema, edema) was observed on treatment of skin with terpenes including FSK. FT-IR, DSC, and histopathological studies revealed that FSK enhanced the skin permeation of the active drug by disruption and extraction of lipid bilayers of SC in consonance with other terpenes.The objective of the present study was to investigate the effect of various terpenes, including a diterpene, forskolin (FSK; a putative penetration enhancer), on skin permeation of valsartan. Permeation studies were carried out with Automated Transdermal Diffusion Cells Sampling System (SFDC 6, LOGAN Instruments Corp., NJ, USA) through rat skin and human cadaver skin (HCS) using ethanol: IPB (pH 7.4) (40:60) as vehicle. The efficacy of the study terpenes for permeation of valsartan across rat skin and human cadaver skin was found in the order of cineole > d-limonene > l-menthol > linalool > FSK and cineole > d-limonene > linalool > l-menthol > FSK, respectively. No apparent skin irritation (erythema, edema) was observed on treatment of skin with terpenes including FSK. FT-IR, DSC, and histopathological studies revealed that FSK enhanced the skin permeation of the active drug by disruption and extraction of lipid bilayers of SC in consonance with other terpenes.

Basil Oil is a Promising Skin Penetration Enhancer for Transdermal Delivery of Labetolol Hydrochloride

Thepresent work investigates effectiveness of basil oil, a volatile oil containing alcoholic terpenes, as a potential penetration enhancer for improved skin permeation of labetolol hydrochloride (LHCl) with reference to camphor, geraniol, thymol, and clove oil. Saturation solubilities of LHCl were determined in water, vehicle (ethanol:water, 60:40 v/v) and vehicle containing 5% w/v terpenes. Comparable (P > 0.05) saturation solubilities were found suggesting an insignificant increase in LHCl flux across rat skin on account of thermodynamic activity. Permeation of LHCl in vehicle per se and in presence of 5% w/v enhancer was investigated by performing in vitro rat abdominal skin permeation studies using a side-by-side glass diffusion cell. Various parameters viz. steady state flux, permeability coefficient, lag time, partition coefficient, diffusion coefficient, and enhancement ratios (ER) were calculated from the permeation data. Basil oil produced the maximum enhancement (ER = 46.52) over neat vehicle, among all enhancers. Activation energies for LHCl permeation in water, vehicle per se and in presence of 5% w/v basil oil were found to be 23.16, 18.71, and 10.98 kcal/mole, respectively. Lowering of activation energy in presence of basil oil suggests creation of new polar pathways in the skin for enhanced permeation of LHCl. Basil oil is proposed as a promising penetration enhancer for improved transdermal drug delivery of labetolol.

Contact lenses in ocular therapeutics

Drug delivery is a difficult task in the field of ocular therapeutics. Owing to the physiological and anatomical constraints of the eye, it is difficult to obtain the correct therapeutic concentration of a drug at the required site of action. This has led to clinicians recommending frequent dosing, which has resulted in noncompliance by patients and decreased cost effectiveness. To overcome these barriers, scientists have explored novel ocular delivery systems, such as in situ gels, ocuserts, nanoparticles and liposomes. A particularly novel form of such a delivery system are contact lenses, which are thin, curved plastic disks that are designed to cover the cornea and which cling to the surface of the eye owing to surface tension. In this article, we describe the introductory literature on ocular delivery using contact lenses, their classification and manufacturing process, and recent advances on drug delivery techniques using such lenses.