Development and Optimisation of Spironolactone Nanoparticles for Enhanced Dissolution Rates and Stability

Stable solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) formulations to enhance the dissolution rates of poorly soluble drug spironolactone (SP) were being developed. Probe ultra-sonication method was used to prepare SLNs and NLCs. All NLCs contained stearic acid (solid lipid carrier) and oleic acid (liquid lipid content), whereas, SLNs were prepared and optimised by using the solid lipid only. The particles were characterised in terms of particle size analysis, thermal behaviour, morphology, stability and in vitro release. The zeta sizer data revealed that the increase in the concentration of oleic acid in the formulations reduced the mean particle size and the zeta potential. The increase in concentration of oleic acid from 0 to 30% (w/w) resulted in a higher entrapment efficiency. All nanoparticles were almost spherically shaped with an average particle size of about ～170 nm. The DSC traces revealed that the presence of oleic acid in the NLC formulations resulted in a shift in the melting endotherms to a higher temperature. This could be attributed to a good long-term stability of the nanoparticles. The stability results showed that the particle size remained smaller in NLC compared to that of SLN formulations after 6 months at various temperatures. The dissolution study showed about a 5.1- to 7.2-fold increase in the release of the drug in 2 h compared to the raw drug. Comparing all nanoparticle formulations indicated that the NLC composition with a ratio of 70:30 (solid:liquid lipid) is the most suitable formulation with desired drug dissolution rates, entrapment efficiency and physical stability.     

Preparation of solid lipid nanoparticles as drug carriers for levothyroxine sodium with in vitro drug delivery kinetic characterization

The aim of this work was to produce and characterize solid lipid nanoparticles (SLN) containing levothyroxine sodium for oral administration, and to evaluate the kinetic release of these colloidal carriers. SLNs were prepared by microemulsion method. The particle size and zeta potential of levothyroxine sodium-loaded SLNs were determined to be around 153 nm,?43 mV (negatively charged), respectively by photon correlation spectroscopy. The levothyroxine entrapment efficiency was over 98 %. Shape and surface morphology were determined by TEM and SEM. They revealed fairly spherical shape of nanoparticles.SLN formulation was stable over a period of 6 months. There were no significant changes in particle size, zeta potential and polydispersity index and entrapment efficiency, indicating that the developed SLNs were fairly stable.     

Clobetasol propionate solid lipid nanoparticles cream for effective treatment of eczema: formulation and clinical implications

In the present study clobetasol propionate (Cp) was loaded as solid lipid nanoparticles (SLN), incorporated it in suitable cream base and evaluated in vitro and its performance clinically against equivalent marketed formulation. Cp was incorporated into SLN by high-pressure homogenization technique and characterized for mean particle size, surface morphology and per cent drug entrapment. Drug permeation and skin uptake studies from Cp creams were carried out in a validated Franz static diffusion cell across human cadaver skin (HCS). Sixteen chronic eczema patients were enrolled in a controlled double blind clinical trial. Optimized Cp-SLN was smooth and spherical under scanning electron microscopy; with average particle size of 177 nm and per cent drug entrapment of 92.05%. In vitro permeation studies revealed lower mean flux value and higher skin uptake of Cp from Cp-SLN cream compared to marketed drug cream. Both formulations were found to be responsive to manifestations of chronic eczema, while Cp-SLN cream prepared in this investigation registered significant improvement in therapeutic response (1.9 fold; inflammation, 1.2 fold; itching) in terms of per cent reduction in degree of inflammation and itching against marketed cream. Further clinical trials are required to ascertain the efficiency of the present formulation.     

Development and characterization of a novel controlled release drug delivery system based on nanostructured lipid carriers gel for meloxicam

Aim

The main objective of the current investigation was to develop nanostructured lipid carriers (NLC) based gel for the enhancement of transdermal absorption of meloxicam (MLX) to achieve local as well as systemic drug action without concurrent gastrointestinal toxicity.

Main methods

NLC gel containing MLX was prepared and characterized for particle size, polydispersity, zeta potential, pH, rheology, entrapment efficiency, occlusion factor, and thermal behavior. In vitro drug release, in vitro skin permeation and deposition studies were carried out using Franz diffusion cells. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) of MLX-NLC gel treated stratum corneum (SC) were undertaken to get an insight into the skin permeation enhancement mechanism of MLX-NLC gel. Toxicity potential of the developed gel formulation was assessed by in vitro hemolysis and histopathological examinations. The rat paw edema test was performed to evaluate the anti-inflammatory activity of MLX-NLC gel.

Key findings

MLX-NLC gel demonstrated sustained release and enhanced the skin permeation and deposition of meloxicam especially into the dermis in comparison to meloxicam gel (control). MLX-NLC had an impact on the barrier properties of the skin and acted via protein and lipid modifications in the stratum corneum. MLX-NLC gel turned out to be hemocompatible, non-irritant, and non toxic with significant anti-inflammatory activity.

Significance

The results suggest that NLC gel could be a promising carrier for the transdermal delivery of meloxicam.     

Topical Delivery of Fenoprofen Calcium <Emphasis Type="Italic">via</Emphasis> Elastic Nano-vesicular Spanlastics: Optimization Using Experimental Design and <Emphasis Type="Italic">In Vivo</Emphasis> Evaluation

The aim of this study was to investigate the potential of surfactant-based nanovesicular system (spanlastics) for topical delivery of fenoprofen calcium (FPCa) to eliminate its oral gastrointestinal adverse effects. FPCa-loaded spanlastics were prepared by thin film hydration (TFH) technique according to a full factorial design to investigate the influence of formulation variables on the drug entrapment efficiency (%EE), particle size (PS), deformability index (DI), and the % drug released after 24 h through the cellulose membrane (Q24h) using Design-Expert® software. The optimized formula (composed of Span 60 and Tween 60 as an edge activator at weight ratio of 8: 2 in presence of Transcutol P as a cosolvent in the hydration media) exhibited the highest %EE (49.91 ± 2.60%), PS of 536.1 ± 17.14 nm, DI of 5.07 ± 0.06 g, and Q24h of 61.11 ± 2.70%; it was also characterized for morphology and physical stability. In vitro release study of FPCa-loaded spanlastic gel and conventional FPCa gel through a synthetic membrane and hairless rat skin were evaluated. The skin permeation study revealed that spanlastic gel exhibited both consistent and prolonged action. Finally, the % inhibition of carrageenan-induced rat paw edema of spanlastic gel was three times higher than the conventional FPCa gel after 24 h. In conclusion, spanlastic-based gel could be a great approach for improving topical delivery of fenoprofen calcium, providing both prolonged and enhanced anti-inflammatory activity in the treatment of arthritis.     

Physicochemical Characteristics, Cytotoxicity, and Antioxidant Activity of Three Lipid Nanoparticulate Formulations of Alpha-lipoic Acid

Exogenously supplied alpha-lipoic acid (LA) has proven to be effective as an antioxidant. In an effort to develop a water-soluble formulation for topical administration, LA was formulated in the form of solid lipid nanoparticles (SLN), nanostructure lipid carriers (NLC), and nanoemulsion (NE) and characterized in terms of physical and biological properties. Mean particle size of 113, 110, and 121 nm were obtained for NE, NLC, and SLN, respectively, with narrow size distribution. Zeta potential was approximately in the range of −25 to −40 mV. Disc and spherical structures of nanoparticles were observed by cryo-scanning electron microscopy. Entrapment efficiency of LA in three formulations was found to be more than 70%. After 120 days of storage at 25°C, physical stability of all formulations remained unchanged whereas the entrapment efficiency of SLN and NLC could be maintained, suggesting relative long-term stability. Prolonged release of LA formulation following the Higuchi model was found where a faster release was observed from NE compared with that of SLN and NLC. More than 80% of cell survivals were found up to 1 μM of LA concentrations. Antioxidant activity analysis demonstrated that all LA-loaded formulations expressed antioxidant activity at a similar magnitude as pure LA. These results suggest that chosen compositions of lipid nanoparticles play an important role on drug loading, stability, and biological activity of nanoparticles. Both SLN and NLC demonstrated their potential as alternative carriers for aqueous topical administration of LA.     

Appraisal of Transdermal Water-in-Oil Nanoemulgel of Selegiline HCl for the Effective Management of Parkinson’s Disease: Pharmacodynamic,Pharmacokinetic, and Biochemical Investigations

In the present study, the potential of transdermal nanoemulsion gel of selegiline hydrochloride for the treatment of Parkinson’s disease was investigated. Water-in-oil nanoemulsions were developed by comparing low- and high-energy methods and were subjected to thermodynamic stability tests, in vitro permeation, and characterization studies. In vitro studies indicated that components of nanoemulsion acted as permeation enhancers with highest flux of 3.531 ± 1.94 μg/cm²/h from nanoemulsion SB6 containing 0.5 mg selegiline hydrochloride, 3% distilled water, 21% S _mix (Span 85, Tween 80, PEG 400), and 76% isopropyl myristate by weight. SB6 with the least droplet size of 183.4 ± 0.35 nm, polydispersity index of 0.42 ± 0.06 with pH of 5.9 ± 0.32 and viscosity of 22.42 ± 0.14 cps was converted to nanoemulsion gel NEGS4 (viscosity = 22,200 ± 400 cps) by addition of Viscup160® for ease of application and evaluated for permeation, safety, and pharmacokinetic profile in Wistar rats. It provided enhancement ratio 3.69 times greater than conventional gel. NEGS4 showed 6.56 and 5.53 times increase in bioavailability in comparison to tablet and conventional gel, respectively, along with sustained effect. Therefore, the developed water-in-oil nanoemulsion gel promises to be an effective vehicle for transdermal delivery of selegiline hydrochloride.     

Diazepam-Loaded Solid Lipid Nanoparticles: Design and Characterization

The aim of the present study was to investigate the feasibility of the inclusion of a water-insoluble drug (diazepam, DZ) into solid lipid nanoparticles (SLNs), which offer combined advantages of rapid onset and prolonged release of the drug. This work also describes a new approach to prepare suppositories containing DZ-loaded SLN dispersions, as potential drug carrier for the rectal route. Modified high-shear homogenization and ultrasound techniques were employed to prepare SLNs. The effect of incorporation of different concentrations of Compritol® ATO 888 or Imwitor® 900K and Poloxamer 188 or Tween 80 was investigated. Results showed that varying the type or concentration of lipid matrix or surfactant had a noticeable influence on the entrapment efficiencies, particle size, and release profiles of prepared SLNs. Differential scanning calorimetry and X-ray diffraction measurements showed that the majority of SLNs possessed less ordered arrangements of crystals than the corresponding bulk lipids, which was favorable for increasing the drug loading capacity. Transmission electron microscopy and laser diffractometry studies revealed that the prepared nanoparticles were round and homogeneous and 60% of the formulations were less than 500 nm. Additionally, SLN formulations showed significant (P?in vitro release of DZ from the suppositories prepared using DZ-loaded SLN dispersions (equivalent to 2 mg DZ) was significantly (P?相似文献   

Nanolipidgel for Enhanced Skin Deposition and Improved Antifungal Activity

The purpose of the research was to prepare and evaluate a topical nanolipidgel (NLH) of terbinafine hydrochloride (TRB), an antimycotic agent, for enhanced skin deposition and improved antifungal activity. Topical solid lipid nanoparticles (SLN) based nanolipidgel was formulated and evaluated. TRB-loaded SLNs were formulated by high-pressure homogenization technique. The stable TRB SLN dispersion was incorporated into a gel using 1% Carbopol 980 NF. Rheological evaluation and texture analysis of the TRB NLH was carried out. Skin permeation, skin deposition, antifungal activity, and occlusivity studies of the nanolipidgel formulation were carried out. The safety of the TRB NLH gel was evaluated using acute skin irritation test on New Zealand White rabbits. The SLN dispersion containing 10% of glyceryl monostearate, 3% of Tween 80, and 1% Plurol Oleique was the most stable. The optimized TRB SLN had a particle size and zeta potential value of 148.6 ± 0.305 nm and −20.4 ± 1.2 mV, respectively. TRB NLH had excellent rheological and texture properties to facilitate its topical application. TRB NLH showed increased skin deposition of the drug over plain (3-fold) and marketed TRB formulation (2-fold). TRB NLH had significantly enhanced antifungal activity against Candida albicans. TRB NLH showed efficient occlusivity and was non-irritant to the rabbit skin with no signs of erythema or edema. Solid lipid nanoparticles-based topical nanolipidgel of terbinafine can be an efficient, industrially scalable, and cost-effective alternative to the existing conventional formulations.KEY WORDS: in vitro antifungal activity, rheological analysis of gel, solid lipid nanoparticles, terbinafine, texture analysis of gel     

Preparation and Evaluation of Miconazole Nitrate-Loaded Solid Lipid Nanoparticles for Topical Delivery

The purpose of this study was to prepare miconazole nitrate (MN) loaded solid lipid nanoparticles (MN-SLN) effective for topical delivery of miconazole nitrate. Compritol 888 ATO as lipid, propylene glycol (PG) to increase drug solubility in lipid, tween 80, and glyceryl monostearate were used as the surfactants to stabilize SLN dispersion in the SLN preparation using hot homogenization method. SLN dispersions exhibited average size between 244 and 766 nm. All the dispersions had high entrapment efficiency ranging from 80% to 100%. The MN-SLN dispersion which showed good stability for a period of 1 month was selected. This MN-SLN was characterized for particle size, entrapment efficiency, and X-ray diffraction. The penetration of miconazole nitrate from the gel formulated using selected MN-SLN dispersion as into cadaver skins was evaluated ex-vivo using franz diffusion cell. The results of differential scanning calorimetry (DSC) showed that MN was dispersed in SLN in an amorphous state. The MN-SLN formulations could significantly increase the accumulative uptake of MN in skin over the marketed gel and showed a significantly enhanced skin targeting effect. These results indicate that the studied MN-SLN formulation with skin targeting may be a promising carrier for topical delivery of miconazole nitrate.     

Dry Gel Containing Optimized Felodipine-Loaded Transferosomes: a Promising Transdermal Delivery System to Enhance Drug Bioavailability

Felodipine has a very low bioavailability due to first-pass metabolism. The aim of this study was to enhance its bioavailability by transdermal application. Felodipine-loaded transferosomes were prepared by thin-film hydration using different formulation variables. An optimized formula was designed using statistical experimental design. The independent variables were the used edge activator, its molar ratio to phosphatidylcholine, and presence or absence of cholesterol. The responses were entrapment efficiency of transferosomes, their size, polydispersity index, zeta potential, and percent drug released after 8 h. The optimized formula was subjected to differential scanning calorimetry studies and its stability on storage at 4°C for 6 months was estimated. This formula was improved by incorporation of different permeation enhancers where ex vivo drug flux through mice skin was estimated and the best improved formula was formulated in a gel and lyophilized. The prepared gel was subjected to in vivo study using Plendil® tablets as a reference. According to the calculated desirability, the optimized transferosome formula was that containing sodium deoxycholate as edge activator at 5:1 M ratio to phosphatidylcholine and no cholesterol. The thermograms of this formula indicated the incorporation of felodipine inside the prepared vesicles. None of the tested parameters differed significantly on storage. The lyophilized gel of labrasol-containing formula was chosen for in vivo study. The relative bioavailability of felodipine from the designed gel was 1.7. In conclusion, topically applied lyophilized gel containing felodipine-loaded transferosomes is a promising transdermal delivery system to enhance its bioavailability.     

Transfersomal Nanoparticles for Enhanced Transdermal Delivery of Clindamycin

The aim of this work was to study the potential of delivering clindamycin phosphate, as an efficient antibiotic drug, into a more absorbed, elastic ultradeformable form, transfersomes (TRSs). These vesicles showed an enhanced penetration through ex vivo permeation characters. TRSs were prepared using thin-film hydration method. Furthermore, they were evaluated for their entrapment efficiency, size, zeta potential, and morphology. Also, the prepared TRSs were converted into suitable gel formulation using carbopol 934 and were evaluated for their gel characteristics like pH, viscosity, spreadability, homogeneity, skin irritation, in vitro release, stability, and ex vivo permeation studies in rats. TRSs were efficiently formulated in a stable bilayer vesicle structure. Furthermore, clindamycin phosphate showed higher entrapment efficiency within the TRSs reaching about 93.3%?±?0.8 and has a uniform particle size. Moreover, the TRSs surface had a high negative charge which indicated the stability of the produced vesicles and resistance of aggregation. Clindamycin phosphate showed a significantly higher in vitro release (p?<?0.05; ANOVA/Tukey) compared with the control carbopol gel. Furthermore, the transfersomal gel showed a significantly higher (p?<?0.05; ANOVA/Tukey) cumulative amount of drug permeation and flux than both the transfersomal suspension and the control carbopol gel. In conclusion, the produced results suggest that TRS-loaded clindamycin are promising carriers for enhanced dermal delivery of clindamycin phosphate.     

Systematic Development of Transethosomal Gel System of Piroxicam: Formulation Optimization, <Emphasis Type="Italic">In Vitro</Emphasis> Evaluation,and <Emphasis Type="Italic">Ex Vivo</Emphasis> Assessment

Piroxicam is used in the treatment of rheumatoid arthritis, osteoarthritis, and other inflammatory diseases. Upon oral administration, it is reported to cause ulcerative colitis, gastrointestinal irritation, edema and peptic ulcer. Hence, an alternative delivery system has been designed in the form of transethosome. The present study describes the preparation, optimization, characterization, and ex vivo study of piroxicam-loaded transethosomal gel using the central composite design. On the basis of the prescreening study, the concentration of lipids and ethanol was kept in the range of 2–4% w/v and 0–40% v/v, respectively. Formulation was optimized by measuring drug retention in the skin, drug permeation, entrapment efficiency, and vesicle size. Optimized formulation was incorporated in hydrogel and compared with other analogous vesicular (liposomes, ethosomes, and transfersomes) gels for the aforementioned responses. Among the various lipids used, soya phosphatidylcholine (SPL 70) and ethanol in various percentages were found to affect drug retention in the skin, drug permeation, vesicle size, and entrapment efficiency. The optimized batch of transethosome has shown 392.730 μg cm^?2 drug retention in the skin, 44.312 μg cm^?2 h^?1 drug permeation, 68.434% entrapment efficiency, and 655.369 nm vesicle size, respectively. It was observed that the developed transethosomes were found superior in all the responses as compared to other vesicular formulations with improved stability and highest elasticity. Similar observations were noted with its gel formulation.     

Evaluation of Meloxicam-Loaded Cationic Transfersomes as Transdermal Drug Delivery Carriers

The aim of this study is to develop meloxicam (MX)-loaded cationic transfersomes as skin delivery carriers and to investigate the influence of formulation factors such as cholesterol and cationic surfactants on the physicochemical properties of transfersomes (i.e., particle size, size distribution, droplet surface charge and morphology), entrapment efficiency, stability of formulations and in vitro skin permeation of MX. The transfersomes displayed a spherical structure. Their size, charge, and entrapment efficiency depended on the composition of cholesterol and cationic surfactants in the formulation. Transfersomes provided greater MX skin permeation than conventional liposomes and MX suspensions. The penetration-enhancing mechanism of skin permeation by the vesicles prepared in this study may be due to the vesicle adsorption to and/or fusion with the stratum corneum. Our results suggest that cationic transfersomes may be promising dermal delivery carriers of MX.     

Topical delivery and in vivo antileishmanial activity of paromomycin-loaded liposomes for treatment of cutaneous leishmaniasis

The present study aimed to evaluate the potential of liposomes loaded with paromomycin (PA), an aminoglycoside antibiotic associated with poor skin penetration, for the topical treatment of cutaneous leishmaniasis (CL). Fluid liposomes were prepared and characterized for particle size, zeta potential, and drug entrapment. Permeation studies were performed with two in vitro models: intact and stripped skin. The antileishmanial activity of free and liposomal PA was evaluated in BALB/c mice infected by Leishmania (L.) major. Drug entrapment ranged from 10 to 14%, and the type of vesicle had little influence on this parameter. Particle size and polydispersity index of the vesicles composed by phosphatidylcholine (PC) and PC/cholesterol (Chol) ranged from of 516 to 362?nm and 0.7 to 0.4, respectively. PA permeation across intact skin was low, regardless of the formulation tested, while drug penetration into skin (percent of the applied dose) from PC (7.2?±?0.2%) and PC/Chol (4.8?±?0.2%) liposomes was higher than solution (1.9?±?0.1%). PA-loaded liposomes enhanced in vitro drug permeation across stripped skin and improved the in vivo antileishmanial activity in experimentally infected mice. Our findings suggest that the liposomes represent a promising alternative for the topical treatment of CL using PA.     

Formulation and <Emphasis Type="Italic">In vitro</Emphasis> Characterization of Eudragit® L100 and Eudragit® L100-PLGA Nanoparticles Containing Diclofenac Sodium

The aim of this study was to formulate and characterize Eudragit® L100 and Eudragit® L100-poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing diclofenac sodium. Diclofenac generates severe adverse effects with risks of toxicity. Thus, nanoparticles were prepared to reduce these drawbacks in the present study. These nanoparticles were evaluated for surface morphology, particle size and size distribution, percentage drug entrapment, and in vitro drug release in pH 6.8. The prepared nanoparticles were almost spherical in shape, as determined by atomic force microscopy. The nanoparticles with varied size (241–274 nm) and 25.8–62% of entrapment efficiency were obtained. The nanoparticles formulations produced the release profiles with an initial burst effect in which diclofenac sodium release ranged between 38% and 47% within 4 h. The extent of drug release from Eudragit® L100 nanoparticles was up to 92% at 12 h. However, Eudragit®/PLGA nanoparticles showed an initial burst release followed by a slower sustained release. The cumulative release at 72 h was 56%, 69%, and 81% for Eudragit®/PLGA (20:80), Eudragit®/PLGA (30:70) and Eudragit®/PLGA (50:50) nanoparticles, respectively. The release profiles and encapsulation efficiencies depended on the amount of Eudragit in the blend. These data demonstrated the efficacy of these nanoparticles in sustaining the diclofenac sodium release profile.     

Experimental study and mathematical modeling for encapsulation of fentanyl citrate drug in nanostructured lipid carrier

Abstract

The aim of this study is to prepare a nanostructured lipid carrier (NLC) containing Fentanyl Citrate drug. The materials were selected in a way to achieve a nanostructure with lower particle size and higher drug entrapment efficiency. For this purpose, we used two mathematical models, Van Krevelen-Hoftyze and Hoy’s methods, which are based on the calculation of solubility parameters. Various NLC formulations are prepared experimentally to validate the mathematical modeling results. Hot homogenization method was used for NLC preparation. DLS, HPLC, TEM and DSC analyses are performed to calculate the size, drug entrapment efficiency, morphology and thermal behavior of particles, respectively. Experimental results suggest that the best NLC formulation has a particle size of 90?nm with a spherical morphology and drug entrapment efficiency of about 82%. A comparison of the mathematical and experimental results exhibits that Van Krevelen-Hoftyzer method is unable to provide an accurate estimation of the decreasing trend of particle size by chaining the components of NLC. However, Hoy’s method seems to be suitable for this purpose. Moreover, both mathematical methods could successfully estimate variation trend of drug entrapment efficiency by chaining the NLC components. Results show that surfactants-lipids solubility parameter has a bearing on the nanoparticle size while drug-lipid solubility parameter affects drug entrapment efficiency.

Communicated by Ramaswamy H. Sarma     

Gastroretentive Microsponge as a Promising Tool for Prolonging the Release of Mitiglinide Calcium in Type-2 Diabetes Mellitus: Optimization and Pharmacokinetics Study

Diabetes mellitus is one of the leading causes of death due to the persistent hyperglycemia that leads to potential complications. Lack of patients’ adherence to their prescribed medication regimens, due to the requirement of frequent dosing, leads to failure of 40–50% of patients to manage their disease. Thus, microsponges of the novel short half-life mitiglinide calcium (MTG) were formulated using Quasi-emulsion solvent diffusion method, employing Eudragit RS100, ethyl cellulose, and polyvinyl alcohol, then characterized in terms of production yield, entrapment efficiency, particle size, in vitro buoyancy, in vitro drug release, and in vivo pharmacokinetics in rabbits. Optimization was done using response surface methodology; the optimized formulation was investigated by FTIR, DSC, and SEM. Results revealed that the optimized MTG microsponge was successfully formulated with high production yield (61.61%?±?0.6), entrapment efficiency (77.7% ±1.37), and particle size of 192.76 μm and it remained buoyant over simulated gastric fluid for 24 h with high percentage of in vitro buoyancy (91.01%?±?2.5). Moreover, it sustained the in vitro drug release with cumulative % release of 83.74?±?1.5 after 24 h. This microsponge was highly porous in nature with interconnected pores where MTG was entrapped with good compatibility as confirmed by SEM, DSC, and FTIR analysis; Pharmacokinetic studies showed improvement in C_max and AUC_0-∞ (1.92- and 20.68-fold, respectively) with marked prolongation in MRT and t_1/2 (7.22- and 7.97-fold, respectively) than the marketed tablet. Thus, it is a promising approach to improve diabetic patients’ compliance by eliminating the necessity of frequent dosing thus attaining better diabetes control.     

Enhanced skin targeting of retinoic acid spanlastics: in vitro characterization and clinical evaluation in acne patients

Abstract

Acne vulgaris is the most common dermatological disorder affecting millions of individuals. Acne therapeutic solutions include topical treatment with retinoic acid (RA) which showed a good efficacy in treatment of mild and moderate cases. However, the high prevalence of adverse events, such as skin dryness, shedding and skin irritation affects the patient convenience and obstruct the acne treatment. Thus, the objective of this paper was to produce Span 60 based elastic vesicles enriched with penetration enhancers, and study their influence on the delivery of RA and its skin irritation. RA-loaded nanovesicles, enriched with Transcutol^®/Labrasol^®, were made using the thin film hydration technique, and assessed for entrapment efficiency, particle size and zeta potential. The optimized RA-loaded nanovesicles (composed of Span 60-Tween 20, and Transcutol^®) were morphologically assessed via transmission electron microscopy. Moreover, RA deposition into newborn mice skin was assessed in vitro under non-occlusive conditions, where the optimized RA-loaded nanovesicles showed 2-fold higher RA deposition in the skin compared to the corresponding one lacking Transcutol. The optimized RA-loaded nanovesicles incorporated into 1% carbopol gel was evaluated for in-vivo clinical performance in acne patients, and showed appreciable advantages over the marketed formulation (Acretin^®) in the treatment of acne regarding skin tolerability and patient’s compliance.     

Ocular Disposition of ∆<Superscript>8</Superscript>-Tetrahydrocannabinol from Various Topical Ophthalmic Formulations

The purposes of this project are to enhance the trans-membrane penetration of Δ⁸-Tetrahydrocannabinol (Δ⁸-THC) and to study the effect of various lipid based systems in delivering the compound, non-invasively, to anterior and posterior ocular chambers. Solid lipid nanoparticles (SLNs), fast gelling films were manufactured using high pressure homogenization and melt cast techniques, respectively. The formulations were characterized for drug content, entrapment efficiency, particle size and subsequently evaluated in vitro for trans-corneal permeation. In vivo, the drug disposition was tested via topical administration in albino rabbits. The eye globes were enucleated at the end of experiment and tissues were analyzed for drug content. All formulations showed favorable physicochemical characteristics in terms of particle size, entrapment efficiency, and drug content. In vitro, the formulations exhibited a transcorneal flux that depended on the formulation’s drug load. An increase in drug load from 0.1 to 0.75% resulted in 12- to16-folds increase in permeation. In vivo, the film was able to deliver THC to all the tissues with high accumulations in cornea and sclera. The SLNs showed a greater ability in delivering THC to all the tissues, at a significantly lower drug load, due to their colloidal size range, which in turn enhanced corneal epithelial membrane penetration. The topical formulations evaluated in the present study were able to successfully deliver Δ⁸-THC in therapeutically meaningful concentrations (EC₅₀ values for CB₁: 6 nM and CB₂: 0.4 nM) to all ocular tissues except the vitreous humor, with pronounced tissue penetration achieved using SLNs as a Δ⁸-THC delivery vehicle.