Vesicular systems for delivering conventional small organic molecules and larger macromolecules to and through human skin

The history of using vesicular systems for drug delivery to and through skin started nearly three decades ago with a study utilizing phospholipid liposomes to improve skin deposition and reduce systemic effects of triamcinolone acetonide. Subsequently, many researchers evaluated liposomes with respect to skin delivery, with the majority of them recording localized effects and relatively few studies showing transdermal delivery effects. Shortly after this, Transfersomes were developed with claims about their ability to deliver their payload into and through the skin with efficiencies similar to subcutaneous administration. Since these vesicles are ultradeformable, they were thought to penetrate intact skin deep enough to reach the systemic circulation. Their mechanisms of action remain controversial with diverse processes being reported. Parallel to this development, other classes of vesicles were produced with ethanol being included into the vesicles to provide flexibility (as in ethosomes) and vesicles were constructed from surfactants and cholesterol (as in niosomes). Thee ultradeformable vesicles showed variable efficiency in delivering low molecular weight and macromolecular drugs. This article will critically evaluate vesicular systems for dermal and transdermal delivery of drugs considering both their efficacy and potential mechanisms of action

ENHANCEMENT OF DISSOLUTION RATE OF HYDROCHLOROTHIAZIDE

Objective: The aim of this study was to enhance the dissolution rate of hydrochlorothiazide (HCTZ).Methods: Binary solid dispersions (SDs) of HCTZ with increasing weight ratios of poloxamer 407, polyethylene glycol 6000 (PEG 6000) or gelucire 50/13 were prepared by solvent evaporation technique. The solid dispersions were deposited on the surface of aerosil 200 to produce a dry product with large surface area. The SDs were characterized with respect to drug dissolution. The mechanism of dissolution enhancement was researched using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC).Results: The unprocessed drug showed erratic, slow dissolution which can be explained on the basis of its hydrophobic nature. Preparation of SDs with hydrophilic carriers resulted in a significant increase in the dissolution rate with most of the drug being liberated in the first 5 min. The dissolution pattern of the drug from the prepared SDs depends mainly on the type of polymer used, and the best dissolution pattern was observed in the SD prepared using 1:1 ratio of the drug to gelucire 50/13 in the presence of aerosil 200 as a carrier. FTIR studies revealed no interaction between the drug and polymers. DSC showed a change in the crystalline structure of the drug after SDs formation. This change can explain the recorded dissolution enhancement.Conclusion: The study presented a system capable of increasing the dissolution rate of HCTZ using polymers which can increase the intestinal permeability as well.Keywords: Hydrochlorothiazide, Poloxamer 407, PEG 6000, Gelucire 50/13, Solid dispersion, Dissolutio

INTESTINAL ABSORPTION OF EPROSARTAN MESYLATE FROM SELF EMULSIFYING SYSTEM AND CYCLODEXTRIN COMPLEX

Objective: The aim of this work was to determine the intestinal membrane transport parameters of eprosartan mesylate (EM) and to investigate self-nano emulsifying drug delivery systems (SNEDDS) and inclusion complexation with hydroxypropyl b cyclodextrin (HPbCD) for enhanced intestinal absorption of eprosartan mesylate. Methods: The intestinal absorption was monitored using the in situ rabbit intestinal perfusion technique. SNEDDS was developed using labrafil, Lauroglycol with a tween in the presence of ethanol. Inclusion complexation was achieved by construction of phase solubility diagram in the presence of HPbCD. The prepared complex was evaluated using Fourier Transform Infrared Spectroscopy (FTIR) and differential scanning calorimetry (DSC). Results: The drug was found to be poorly absorbed from the jejuno-ileum and the colon with the absorption being mainly through paracellular pathway. An inclusion complex was developed between the drug and HPβCD. Perfusion of the drug in the nanoemulsion formulation or as an inclusion complex resulted in a significant increase in the intestinal absorption of the drug compared with the control.Conclusion: SNEDDS and inclusion complexation are promising strategies for enhanced intestinal absorption of eprosartan mesylate

Penetration enhancers in proniosomes as a new strategy for enhanced transdermal drug delivery

AbstractThe aim of this work is to investigate penetration enhancers in proniosomes as a transdermal delivery system for nisoldipine. This was performed with the goal of optimising the composition of proniosomes as transdermal drug delivery systems. Plain proniosomes comprising sorbitan monostearate, cholesterol, ethanol and a small quantity of water were initially prepared. Subsequently, proniosomes containing lecithin or skin penetration enhancers were prepared and evaluated for transdermal delivery of nisoldipine. The plain proniosomes significantly enhanced the transdermal flux of nisoldipine to reach 12.18μgcm−2h−1 compared with a saturated aqueous drug solution which delivered the drug at a rate of 0.46μgcm−2h−1. Incorporation of lecithin into such proniosomes increased the drug flux to reach a value of 28.51μgcm−2h−1. This increase can be attributed to the penetration enhancing effect of lecithin fatty acid components. Replacing lecithin oleic acid (OA) produced proniosomes of comparable efficacy to the lecithin containing system. The transdermal drug flux increased further after incorporation of propylene glycol into the OA based proniosomes. Similarly, incorporation of isopropyl myristate into plain proniosomes increased drug flux. The study introduced enhanced proniosomes as a promising transdermal delivery carrier and highlighted the role of penetration enhancing mechanisms in enhanced proniosomal skin delivery. The study opened the way for another line of optimisation of niosome proconcentrates

Effect of water-in-oil microemulsions and lamellar liquid crystalline systems on the precorneal tear film of albino New Zealand rabbits

The aim of this study is to investigate the effect of phase transition water-in-oil (w/o) microemulsions (ME) and liquid crystalline systems (LC) on the precorneal tear film (PCTF). The study used six albino NZ rabbits and monitored the integrity and stability of the PCTF before and after instillation of test formulations. The effects were evaluated by assessment of the PCTF lipid layer using interferometry, tear evaporation rate measurements, and indirect estimation of tear volume. Ocular application of test formulations changed the appearance of the PCTF lipid layer, indicating lipid layer disruption. The recovery time was longer in case of ME compared with an aqueous solution (SOL). The tear evaporation rate was increased after application of both ME and LC systems compared with the SOL, with the LC system showing the greatest effect. Tear volume measurement results revealed minimal changes associated with the instillation of both ME systems. Whilst phase transition w/o ME systems can interact with the PCTF lipid layer in albino New Zealand rabbits, their effect on the volume of resident tears was found to be minimal

Smart liquids for oral controlled drug release: An overview of alginate and non-alginate based systems

Sustaining and controlling the rate of drug release is essential in pharmaceutical technology. It can reduce the number of units administered by the patient with subsequent improvement in patient compliance. These technologies can allow controlled liberation of the active pharmaceutical ingredients to correlate with the chronobiology of the diseases. The significance can be hastened if the controlled release technology was adopted in liquid oral dosage form. Numerous approaches have been implemented in development of liquid oral controlled release formulations. These include preparation of sustained release coated microparticles which are fabricated in the form of oral suspension. Application of ion exchange resin showed success with some products available in the market. Alginate based in situ gelling system has gained much interest. This system depends on fabrication of drug in alginate solution in presence of sequestered calcium ions. This system undergoes in-situ gelation immediately after administration due to liberation of calcium ion in the acidic environment of the stomach. The developed gel may be manipulated to float or to perform mucoadhesion. The promise of such technique has been magnified further after combination with chitosan which maintained gel formation in the stomach as well as in the intestinal environment. This article will provide an overview on liquid oral controlled release drug delivery systems with emphasis on the alginate based formulations

Comparison of the early cardiac electromechanical remodeling following transcatheter and surgical secundum atrial septal defect closure in adults

Abstract Background Secundum atrial septal defect (ASD) closure leads to electrical and mechanical remodeling that occurs early after shunt disappearance. The relationship between electromechanical remodeling using electrocardiogram (ECG) and cardiac magnetic resonance (CMR) after percutaneous and surgical closure has not yet been recorded in prospective studies. Objective We thought to study right atrium (RA) and right ventricle (RV) changes by CMR 3 months after transcatheter and surgical closure and their comparison with electrical remodeling by ECG. Results We prospectively evaluated 30 consecutive adult patients with isolated secundum ASD who were referred for (transcatheter and surgical) ASD closure. There was significant reduction in all of the electrical parameters within the same group as compared to the baseline values, except P wave dispersion (Pd). (P max was 97.33 ± 16.67 (pre closure) to 76 ± 15.49 (post closure) in the device group and 97.33 ± 12.79 (preclosure) to 73.33 ± 16.32 (post closure) in the surgical group, QRS complex was 104 ± 18.82 (preclosure) to 80 ± 18.51 (post closure) in the device group and 106.67 ± 14.47 (preclosure) to 86.67 ± 17.99 (post closure) in the surgical group. QTc maximum was 478.53 ± 36.79 (preclosure) to 412.53 ± 38.03 (post closure) in the device group and 470.53 ± 65.70 (preclosure) to 405.93 ± 63.08 (post closure) in the surgical group, and QTc dispersion was 70.33 ± 24.04 (preclosure) to 60.26 ± 28.56 (post closure) in the device group and 80.73 ± 30.38 (preclosure) to 60.27 ± 28.57 (post closure) in the surgical group).There was no significant difference between two groups indicating that transcatheter and surgical closure had led to equivalent value of electrical remodeling. In CMR study, we measured RA maximal volume and right ventricle end diastolic volume (RVEDV), RA maximal volume decreased significantly as compared to the base line values post closure in both groups (P value < 0.001). The reduction in RA max volume was more in the transcatheter closure group; however, this difference was not statistically significant when compared with the surgical arm (P value = 0.5).RVEDV decreased significantly in both groups as compared to the baseline values (P value < 0.001). Transcatheter closure resulted in more significant reduction in the RVEDV than the surgical closure (P value = 0.03). Conclusion Our study showed early significant electromechanical reverse remodeling in most of the study parameters from the baseline values after ASD closure. We found no significant differences in all of the electrical and RA mechanical remodeling parameters with significantly better mechanical remodeling of RV in the device group