Faiyaz Shakeel

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.

Design, development and evaluation of novel nanoemulsion formulations for transdermal potential of celecoxib

Design, development and evaluation of novel nanoemulsion formulations for transdermal potential of celecoxib The aim of the present study was to investigate the potential of nanoemulsion formulations for transdermal delivery of celecoxib (CXB). The in vitro skin permeation profile of optimized formulations was compared with CXB gel and nanoemulsion gel. Significant increase in the steady state flux (Jss), permeability coefficient (Kp) and enhancement ratio (Er) was observed in nanoemulsion formulations T1 and T2 (p < 0.05). The highest value of these permeability parameters was obtained in formulation T2, which consisted of 2% (m/m) of CXB, 10% (m/m) of oil phase (Sefsol 218 and Triacetin), 50% (m/m) of surfactant mixture (Tween-80 and Transcutol-P) and 40% (m/m) water. The anti-inflammatory effects of formulation T2 showed a significant increase (p < 0.05) in inhibition after 24 h compared to CXB gel and nanoemulsion gel on carrageenan-induced paw edema in rats. These results suggested that nanoemulsions are potential vehicles for improved transdermal delivery of CXB. Dizajn, razvoj i vrednovanje novih nanoemulzija za transdermalnu primjenu celekoksiba U radu su opisana ispitivanja nanoemulzija za transdermalnu primjenu celekoksiba (CXB). Profil permeacije kroz kožu ispitivan je in vitro i uspoređivan sa CXB gelom i nanoemulzijskim gelom. U formulacijama T1 i T2 postignuto je značajno povećanje ustaljenog fluksa (Jss), koeficijenta permeabilnosti (Kp) i povećanje omjera (Er) (p < 0.05). Najveće vrijednosti parametara permeabilnosti dobivene su u formulaciji T2 koja je sadržala 2% m/m CXB, 10% m/m uljne faze (Sefsol 218 i Triacetin), 50% m/m površinski-aktivnih tvari (Tween-80 i Transcutol-P) i 40% m/m vode. Protuupalno djelovanje formulacije T2 na edem šape štakora uzrokovan karageninom značajno je povećano (p < 0.05) poslije 24 h u usporedbi sa CXB gelom i nanoemulzijskim gelom. Rezultati ukazuju na poboljšanu isporuku celekoksiba putem nanoemulzija.

Formulation development and optimization using nanoemulsion technique: a technical note.

Summary and ConclusionRamipril nanoemulsion formulations were successfully prepared by the spontaneous emulsification method (titration method). Sefsol 218 was selected as the oil phase for the development of the formulation on the basis of the solubility studies. The differences in the droplet size between the formulations selected from the phase diagram was not statistically significant, although the polydispersity was at a minimum for the formulation containing 20% oil, 27% Smix, and 53% vol/vol aqueous phase. The droplet size was found to be 34.5 nm. Therefore, nanoemulsion, a multipurpose technology, can be exploited in drug delivery for poorly soluble drugs. Nanoemulsions have a higher solubilization capacity than simple micellar solutions, and their thermodynamic stability offers advantages over unstable dispersions, such as emulsions and suspensions, because they can be manufactured with little energy input (heat or mixing) and have a long shelf life. This technical note explains the basis for calculation and construction of pseudoternary phase diagrams and, most important, explains selection of the formulations from the phase diagrams to avoid metastable formulations having minimum surfactant concentration in the least possible time.

Transdermal delivery of anticancer drug caffeine from water-in-oil nanoemulsions

Recently caffeine has been investigated for the treatment of various types of cancers upon oral administration. There is also some evidence that dermally applied caffeine can protect the skin from skin cancer caused by sun exposure. Therefore nanoemulsion formulation of caffeine for transdermal drug delivery was developed and evaluated in the present investigation. Different w/o nanoemulsion formulations of caffeine were prepared by oil phase titration method. Thermodynamically stable nanoemulsions were characterized for morphology, droplet size, viscosity and refractive index. The in vitro skin permeation studies were performed on Franz diffusion cell using rat skin as permeation membrane. The in vitro skin permeation profile of optimized formulation was compared with aqueous solution of caffeine. Significant increase in permeability parameters was observed in nanoemulsion formulations (P<0.05) as compared to aqueous solution of caffeine. The steady-state flux (J(ss)) and permeability coefficient (K(p)) for optimized nanoemulsion formulation (C12) were found to be 147.55+/-8.21 microg/cm(2)/h and 1.475 x 10(-2)+/-0.031 x 10(-2)cm/h, respectively. Enhancement ratio (E(r)) was found to be 17.37 in optimized formulation C12 compared with other formulations. Overall these results suggested that w/o nanoemulsions are good carriers for transdermal delivery of caffeine.

Skin permeation mechanism and bioavailability enhancement of celecoxib from transdermally applied nanoemulsion

BackgroundCelecoxib, a selective cyclo-oxygenase-2 inhibitor has been recommended orally for the treatment of arthritis and osteoarthritis. Long term oral administration of celecoxib produces serious gastrointestinal side effects. It is a highly lipophilic, poorly soluble drug with oral bioavailability of around 40% (Capsule). Therefore the aim of the present investigation was to assess the skin permeation mechanism and bioavailability of celecoxib by transdermally applied nanoemulsion formulation. Optimized oil-in-water nanoemulsion of celecoxib was prepared by the aqueous phase titration method. Skin permeation mechanism of celecoxib from nanoemulsion was evaluated by FTIR spectral analysis, DSC thermogram, activation energy measurement and histopathological examination. The optimized nanoemulsion was subjected to pharmacokinetic (bioavailability) studies on Wistar male rats.ResultsFTIR spectra and DSC thermogram of skin treated with nanoemulsion indicated that permeation occurred due to the disruption of lipid bilayers by nanoemulsion. The significant decrease in activation energy (2.373 kcal/mol) for celecoxib permeation across rat skin indicated that the stratum corneum lipid bilayers were significantly disrupted (p < 0.05). Photomicrograph of skin sample showed the disruption of lipid bilayers as distinct voids and empty spaces were visible in the epidermal region. The absorption of celecoxib through transdermally applied nanoemulsion and nanoemulsion gel resulted in 3.30 and 2.97 fold increase in bioavailability as compared to oral capsule formulation.ConclusionResults of skin permeation mechanism and pharmacokinetic studies indicated that the nanoemulsions can be successfully used as potential vehicles for enhancement of skin permeation and bioavailability of poorly soluble drugs.

A review on the strategies for oral delivery of proteins and peptides and their clinical perspectives

In the modern world, a number of therapeutic proteins such as vaccines, antigens, and hormones are being developed utilizing different sophisticated biotechnological techniques like recombinant DNA technology and protein purification. However, the major glitches in the optimal utilization of therapeutic proteins and peptides by the oral route are their extensive hepatic first-pass metabolism, degradation in the gastrointestinal tract (presence of enzymes and pH-dependent factors), large molecular size and poor permeation. These problems can be overcome by adopting techniques such as chemical transformation of protein structures, enzyme inhibitors, mucoadhesive polymers and permeation enhancers. Being invasive, parenteral route is inconvenient for the administration of protein and peptides, several research endeavors have been undertaken to formulate a better delivery system for proteins and peptides with major emphasis on non-invasive routes such as oral, transdermal, vaginal, rectal, pulmonary and intrauterine. This review article emphasizes on the recent advancements made in the delivery of protein and peptides by a non-invasive (peroral) route into the body.

Nanoemulsions as potential vehicles for transdermal and dermal delivery of hydrophobic compounds: an overview

Introduction: In recent years, nanoemulsions have been investigated as potential drug delivery vehicles for transdermal and dermal delivery of many compounds especially hydrophobic compounds in order to avoid clinical adverse effects associated with oral delivery of the same compounds. Droplet size and surface properties of nanoemulsions play an important role in the biological behavior of the formulation. Areas covered: In this review, current literature of transdermal and dermal delivery of hydrophobic compounds both in vitro as well as in vivo has been summarized and analyzed. Expert opinion: Nanoemulsions have been formulated using a variety of pharmaceutically acceptable excipients. In many cases of dermal and transdermal nanoemulsions, the skin irritation or skin toxicity issues on human beings have not been considered which needs to be evaluated properly. In the last decade, much attention has been made in exploring new types of nanoemulsion-based drug delivery system for dermal and transdermal delivery of many hydrophobic compounds. This area of research would be very advantageous for formulation scientists in order to develop some nanoemulsion-based formulations for their commercial exploitation and clinical applications.

Celecoxib nanoemulsion: Skin permeation mechanism and bioavailability assessment

The aim of the present study was to assess the skin permeation mechanism and bioavailability of celecoxib (CXB) using novel nanoemulsion formulation. Fourier transform infrared spectra and differential scanning calorimetric thermogram of skin treated with nanoemulsion indicated that permeation occurred due to the extraction of stratum corneum (SC) lipids by nanoemulsion. The significant decrease in activation energy for CXB permeation across rat skin indicated that the SC lipid bilayers were significantly disrupted (p < 0.05). Photomicrograph of skin sample showed the disruption and extraction of lipid bilayers as distinct voids and empty spaces visible in the epidermal region. The absorption of CXB through transdermally applied nanoemulsion and nanoemulsion gel resulted in 3.03- and 2.65-fold increases in bioavailability when compared with conventional oral capsule formulation. Overall, these findings indicated that nanoemulsions can be successfully used for the enhancement of skin permeation and bioavailability of poorly soluble drugs.

Investigation of true nanoemulsions for transdermal potential of indomethacin: characterization, rheological characteristics, and ex vivo skin permeation studies

The aim of the present study was to investigate the potential of true nanoemulsions for transdermal delivery of indomethacin. Thermodynamically stable true nanoemulsions were characterized for morphology using transmission electron microscopy (TEM), droplet size, rheological characteristics, and refractive index. The rheological behavior for all true nanoemulsions was found to be Newtonian as viscosity was unchanged by increasing the rate of shear. The ex vivo skin permeation studies were performed using Franz diffusion cell with rat skin as permeation membrane. The ex vivo skin permeation profile of optimized formulation was compared with marketed Indobene gel and nanoemulsion gel. Significant increase in permeability parameters was observed in nanoemulsion formulations (P < 0.05). The steady-state flux (Jss) and permeability coefficient (Kp) for optimized nanoemulsion formulation were found to be 73.96 ± 2.89 μg/cm2/h and 1.479 × 10−2 ± 0.289 × 10− 2 cm/h, respectively, which were significant compared with Indobene gel and nanoemulsion gel (P < 0.05). Enhancement ratio (Er) was found to be 7.88 in optimized formulation F6 compared with other formulations. These results suggested that nanoemulsions can be used as potential vehicles for improved transdermal delivery of indomethacin.

Proniosomal transdermal therapeutic system of losartan potassium: development and pharmacokinetic evaluation

The purpose of the current study was to investigate the feasibility of proniosomes as transdermal drug delivery system for losartan potassium. Different preparations of proniosomes were fabricated using different nonionic surfactants, such as Span 20, Span 40, Span 60, Span 80, Tween 20, Tween 40, and Tween 80. Different formulae were prepared and coded as PNG-1 (proniosomal gel-1) to PNG-7. The best in vitro skin permeation profile was obtained with proniosomal formulation PNG-2 in 24 h. The permeability parameters such as flux, permeability coefficient, and enhancement ratio were significant for PNG-2 compared with other formulations (P < 0.05). This optimized PNG-2 was fabricated in the form of transdermal patch using HPMC gel as a suitable base. Proniosomal transdermal therapeutic system (PNP-H) was found to be the optimized one as it gave better release of drug and better permeation in a steady-state manner over a desired period of time, that is, 24 h through rat skin. In vivo pharmacokinetic study of PNP-H showed a significant increase in bioavailability (1.93 times) compared with oral formulation of losartan potassium. The formulation appeared to be stable when stored at room temperature (30 ± 2°C) and at refrigeration temperature (4 ± 2°C) for 45 days.