Yasmin Sultana

Liposomal Drug Delivery Systems: An Update Review

The discovery of liposome or lipid vesicle emerged from self forming enclosed lipid bi-layer upon hydration; liposome drug delivery systems have played a significant role in formulation of potent drug to improve therapeutics. Recently the liposome formulations are targeted to reduce toxicity and increase accumulation at the target site. There are several new methods of liposome preparation based on lipid drug interaction and liposome disposition mechanism including the inhibition of rapid clearance of liposome by controlling particle size, charge and surface hydration. Most clinical applications of liposomal drug delivery are targeting to tissue with or without expression of target recognition molecules on lipid membrane. The liposomes are characterized with respect to physical, chemical and biological parameters. The sizing of liposome is also critical parameter which helps characterize the liposome which is usually performed by sequential extrusion at relatively low pressure through polycarbonate membrane (PCM). This mode of drug delivery lends more safety and efficacy to administration of several classes of drugs like antiviral, antifungal, antimicrobial, vaccines, anti-tubercular drugs and gene therapeutics. Present applications of the liposomes are in the immunology, dermatology, vaccine adjuvant, eye disorders, brain targeting, infective disease and in tumour therapy. The new developments in this field are the specific binding properties of a drug-carrying liposome to a target cell such as a tumor cell and specific molecules in the body (antibodies, proteins, peptides etc.); stealth liposomes which are especially being used as carriers for hydrophilic (water soluble) anticancer drugs like doxorubicin, mitoxantrone; and bisphosphonate-liposome mediated depletion of macrophages. This review would be a help to the researchers working in the area of liposomal drug delivery.

Taste Masking Technologies in Oral Pharmaceuticals: Recent Developments and Approaches

Taste is one of the most important parameters governing patient compliance. Undesirable taste is one of several important formulation problems that are encountered with certain drugs. Oral administration of bitter drugs with an acceptable degree of palatability is a key issue for health care providers, especially for pediatric patients. Several oral pharmaceuticals, numerous food and beverage products, and bulking agents have unpleasant, bitter‐tasting components. So, any pharmaceutical formulation with a pleasing taste would definitely be preferred over a competitors product and would translate into better compliance and therapeutic value for the patient and more business and profits for the company. The desire of improved palatability in these products has prompted the development of numerous formulations with improved performance and acceptability. This article reviews the earlier applications and methodologies of taste masking and discusses the most recent developments and approaches of bitterness reduction and inhibition for oral pharmaceuticals.

Review of Ocular Drug Delivery

Successful treatment of eye diseases requires effective concentration of drug at the eye for sufficient period of time. Conventional ocular drug delivery including eye drops, systemic administration, ophthalmic ointments, is no longer sufficient to combat ocular diseases. This article reviews the constraints with conventional ocular therapy, and explores various novel approaches, to improve the ocular bioavailability of drugs to the anterior chamber of the eye.

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.

Preparation, characterization, and evaluation of gatifloxacin loaded solid lipid nanoparticles as colloidal ocular drug delivery system.

This article describes the preparation and characterization of solid lipid nanoparticles (SLNs) prepared with stearic acid (SLN-A) and a mixture of stearic acid and Compritol (SLN-B) as lipid matrix and poloxamer-188 as surfactant, using sodium taurocholate and ethanol as co-surfactant mixture, with a view to applying the SLN in topical ocular drug delivery. The SLNs were prepared by o/w microemulsion technique and characterized by time-resolved particle size analysis, polydispersity index, zeta(ζ )-potential, differential scanning calorimetry (DSC), IR-spectroscopy, and wide-angle X-ray diffractometry (WAXD). The results obtained in these studies were compared with SLN prepared with stearic acid alone. IR, WAXD, and DSC studies revealed low-crystalline SLN and were having positive ζ -potentials after three-months of storage. Results indicated mixed lipid-matrix produced SLN with low-crystallinity and smaller particle sizes and higher drug entrapment compared with SLN prepared with stearic acid alone, therefore SLN-B would be suitable for the preparation of nanosuspension. Nanosuspensions were subjected to rheological and physicochemical evaluation, in vitro drug release and ex vivo corneal permeation studies and their effect were evaluated on corneal hydration-level. SLN composed of stearic acid and compritol would prove to be a good ocular drug delivery system considering the smaller particle size, particle size stability, and physiologically tolerable components.

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.

Ion-Activated, Gelrite®-Based in Situ Ophthalmic Gels of Pefloxacin Mesylate: Comparison with Conventional Eye Drops

The purpose of our work was to develop an ophthalmic delivery system of a flouroquinolone antibiotic, pefloxacin mesylate, based on the concept of ion-activated in situ gelation. Gelrite® gellan gum, a novel ophthalmic vehicle, that gels in the presence of mono- or divalent-cations present in the lacrimal fluid, was used as the gelling agent. The developed formulation was compared with marketed eye drops in efficacy of treatment of bacterial conjunctivitis that was induced artificially in rabbits. The formulations were evaluated for rheological characteristics, in vitro release behavior, antimicrobial efficacy, and efficacy against bacterial conjunctivitis.We found that in situ gelling formulations passed the test for sterility. The formulations exhibited a first-order release pattern over 12 hr in in vitro release studies. The developed formulation was effective against selected micro-organisms in antimicrobial efficacy studies. The shelf lives of formulation was >2 years. The formulation demonstrated better therapeutic efficacy compared with standard eye drops because it improved the clinical parameters monitored for prolonged periods. The developed formulations can be considered as a viable alternative to conventional eye drops.

Enhanced transdermal delivery of an anti-hypertensive agent via nanoethosomes: Statistical optimization, characterization and pharmacokinetic assessment

The aim of the current investigation is to develop and statistically optimize nanoethosomes for transdermal valsartan delivery. Box-Behnken experimental design was applied for optimization of nanoethosomes. The Independent variables were phospholipids 90G (X(1)), ethanol (X(2)), valsartan (X(3)) and sonication time (X(4)) while entrapment efficiency (Y(1)), vesicle size (Y(2)) and flux (Y(3)) were the dependent variables. The optimized formulation obtained was then tested in rats for an in vivo pharmacokinetic study. Results indicate that the nanoethosomes of valsartan provides better flux, reasonable entrapment efficiency, more effectiveness for transdermal delivery as compared to rigid liposomes. Optimized nanoethosomal formulation with mean particle size is 103 ± 5.0 nm showed 89.34 ± 2.54% entrapment efficiency and achieved mean transdermal flux 801.36 ± 21.45 μg/cm(2)/h. Nanoethosomes proved significantly superior in terms of, amount of drug permeated in the skin, with an enhancement ratio of 43.38 ± 1.37 when compared to rigid liposomes. Confocal laser scanning microscopy revealed an enhanced permeation of Rhodamine-Red loaded nanoethosomes to the deeper layers of the skin as compared to conventional liposomes. In vivo pharmacokinetic study of nanoethosomal transdermal therapeutic system showed a significant increase in bioavailability (3.03 times) compared with oral suspension of valsartan. Our results suggest that nanoethosomes are an efficient carrier for transdermal delivery of valsartan.

Enhanced Transdermal Drug Delivery Techniques: An Extensive Review of Patents

Transdermal drug delivery system has been accepted as potential non-invasive route of drug administration, with advantages of avoidance of the first-pass metabolism, sustained therapeutic action and better patient compliance, though, its prevalent use is restricted due to excellent impervious nature of skin. It is the greatest challenge for researchers to surmount the inherent limitations imposed by stratum corneum of skin, for enhanced transdermal drug delivery to achieve systemic therapeutic concentration. Thus, many approaches have been attempted to perturb skin barrier and enhance the transdermal delivery of drug. The major approaches for enhancing transdermal delivery are physical enhancers (ultrasound, iontophoresis, electroporation, magnetophoresis, microneedle), vesicles, particulate systems (liposome, niosome, transfersome, microemulsion, solid lipid nanoparticle) and chemical enhancers (sulphoxides, azones, glycols, alkanols, terpenes etc.). The present review explores recent patents on techniques employed to breach the skin barrier for drug permeation along with their penetration enhancement mechanisms.

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.