Comparative Study on the Effects of Some Polyoxyethylene Alkyl Ether and Sorbitan Fatty Acid Ester Surfactants on the Performance of Transdermal Carvedilol Proniosomal Gel Using Experimental Design

The aim of this work was to investigate the effects of formulation variables on development of carvedilol (CAR) proniosomal gel formulations as potential transdermal delivery systems. Different non-ionic surfactants; polyoxyethylene alkyl ethers, namely Brij 78, Brij 92, and Brij 72; and sorbitan fatty acid esters (Span 60) were evaluated for their applicability in preparation of CAR proniosomal gels. A 2³ full factorial design was employed to evaluate individual and combined effects of formulation variables, namely cholesterol content, weight of proniosomes, and amount of CAR added on performance of proniosomes. Prepared proniosomes were evaluated regarding entrapment efficiency (EE%), vesicle size, and microscopic examination. Also, CAR release through cellulose membrane and permeation through hairless mice skin were investigated. Proniosomes prepared with Brij 72 and Span 60 showed better niosome forming ability and higher EE% than those prepared with Brij 78 and Brij 92. Higher EE% was obtained by increasing both weight of proniosomes and amount of CAR added, and decreasing cholesterol content. Release rate through cellulose membrane was inversely affected by weight of proniosomes. In Span 60 proniosomes, on increasing percent of cholesterol, a decrease in release rate was observed. While in Brij 72 proniosomes, an enhancement in release rate was observed on increasing amount of CAR added. Permeation experiments showed that skin permeation was mainly affected by weight of proniosomes and that Span 60 proniosomal gels showed higher permeation enhancing effect than Brij 72. Proniosomal gel could constitute a promising approach for transdermal delivery of CAR.     

Nano-proniosomes enhancing the transdermal delivery of mefenamic acid

Mefenamic acid (MA) is a BCS II class NSAID drug. It is available only in the form of tablets, capsules, and pediatric suspensions. Oral administration of MA is associated with severe gastrointestinal side effects. The aim of this study was to develop a convenient and low-cost transdermal drug delivery system for MA using proniosome as a novel carrier without the addition of penetration enhancers. The formulation factors, such as the presence of cholesterol, types of lecithin, and surfactants were investigated for their influence on the entrapment efficiency, rate of hydration, vesicle size, and zeta potential, in vitro drug release and skin permeation in order to optimize the proniosomal formulations with the minimum dose of the drug. Furthermore, the in vivo anti-inflammatory effect was evaluated on a formalin-induced rat paw edema model. The results showed that the type of surfactants had higher impact on the entrapment efficiency than the type of lecithins, with the highest in Span 80 (82.84%). The release of MA from Span 80 proniosomal gel was significantly affected by the type of lecithin used. The addition of cholesterol significantly increased both the drug release and the skin permeation flux of MA. Zeta potential showed a stable A4 noisomal suspension. DSC revealed the molecular dispersion of MA into the loaded proniosomes. In vivo study of the treatment group with MA proniosome gel showed a significant inhibition of rat paw edema compared with the same gel without the drug (control). The results of this study suggest that proniosomes are promising nano vesicular carriers and safe alternatives to enhance the transdermal delivery of MA.     

Enhancement of lomefloxacin Hcl ocular efficacy via niosomal encapsulation: in vitro characterization and in vivo evaluation

The aim of this study is to develop and evaluate niosomal dispersions loaded with the hydrophilic drug; lomefloxacin Hcl (LXN) for the management of ocular bacterial conjunctivitis. LXN-loaded niosomes were prepared by the thin film hydration method following a full factorial formulation design. Two independent variables were evaluated: the type of surfactant (X1) and the surfactant:cholesterol ratio (X2). The dependent variables comprised entrapment efficiency (EE%: Y1), particle size (PS: Y2) and zeta potential (ZP: Y3). The optimum formulation, N-LXN14 (Tw60: CH, 1:1), was spherical in shape and exhibited EE% of 68.41?±?0.07, PS of 176.0?±?0.98 and ZP of -40.70?±?2.20 with a sustained release profile over 8?hours following the Higuchi model. N-LXN14 proved good physicochemical stability under refrigeration up to 3 months. Ocular irritancy test showed no signs of ocular toxicity, confirming the safety and suitability for ocular application. Microbiological evaluation of the antibacterial effect of N-LXN14 was conducted using the susceptibility test and through the induction of topical conjunctivitis by Staphylococcus aureus (S. aureus) followed by topical therapy. Susceptibility test manifested significantly higher percent inhibition of S. aureus and higher AUC_0–12?h of N-LXN14 (604.59?±?0.05) compared to the commercial product (126.25?±?0.049). Both clinical observation and colony count of the infected eyes after eight days of treatment demonstrated significant improvement in therapeutic response. The infected eyes were completely healed with eradication of S. aureus. In conclusion, the results showed that LXN niosomal dispersions may serve as a promising superior ocular delivery system in the treatment of bacterial conjunctivitis.     

Sorbitan ester niosomes for topical delivery of rofecoxib

The aim of the present investigation is to encapsulate rofecoxib in niosomes and incorporate the prepared niosomes into dermal gel base for sustained therapeutic action. Niosomes were prepared by lipid film hydration technique and were analyzed for size, entrapment efficiency and drug retention capacity. Niosomal vesicles were then incorporated into blank carbopol gel to form niosomal gel. The in vitro permeation study across pig skin was performed using Keshary-Chien glass diffusion cell. The size and entrapment efficiency of the niosomal vesicles increased with gradual increase in HLB value of nonionic surfactants used. Maximum drug entrapment was observed with Span 20 with HLB value of 8.6 and drug leakage from vesicles was less at refrigerated condition than at the room temperature. Higher proportion of cholesterol made the niosomal formulation more stable with high drug retention properties. The niosomal gel showed a prolong drug release behavior compared to plain drug gel. Differential scanning calorimetric study of drug loaded gel and pig skin after permeation study confirmed inertness of carbopol gel base toward rofecoxib and absence of drug metabolism in the skin during permeation study, respectively. The niosomal formulations were successfully prepared by lipid film hydration technique using cholesterol and Span as nonionic surfactant. Presence of cholesterol made niosomes more stable with high drug entrapment efficiency and retention properties. The lower flux value of niosomal gel as compared to plain drug gel across pig skin assured the prolong drug release behavior with sustained action.     

In Vitro Evaluation of Proniosomes as a Drug Carrier for Flurbiprofen

The purpose of the present investigation is to formulate and evaluate proniosomal transdermal carrier systems for flurbiprofen. Proniosomes were prepared using various non-ionic surfactants, namely span 20 (Sp 20), span 40 (Sp 40), span 60 (Sp 60) and span 80 (Sp 80) without and with cholesterol at percentages ranging from 0% to 50%. The effect of surfactant type and cholesterol content on drug release was investigated. Drug release was tested by diffusion through cellophane membrane and rabbit skin. Drug release from the prepared systems was compared to that from flurbiprofen suspensions in distilled water and HPMC (hydroxypropylmethylcellulose) gels. In case of Sp 20 and Sp 80, the added amount of cholesterol affected the preparation type to be either proniosomal alcoholic solutions or liquid crystalline gel systems. On the other hand, both Sp 40 and Sp 60 produced gel systems in presence or absence of cholesterol. Microscopic observations showed that either proniosomal solutions or gel formulations immediately converted to niosomal dispersions upon hydration. Due to the skin permeation barrier, rabbit skin showed lower drug diffusion rates compared to cellophane membrane. The proniosomal composition controlled drug diffusion rates to be either faster or slower than the prepared flurbiprofen suspensions in HPMC gels or distilled water, respectively. In conclusion, this study demonstrated the possibility of using proniosomal formulations for transdermal drug delivery.     

Formulation and Characterization of Bovine Serum Albumin-Loaded Niosome

Niosomal vesicle, as a unique novel drug delivery system, is synthesized by non-ionic surfactants. Both hydrophilic and lipophilic drugs and also biomacromolecular agents, such as peptides and proteins can be encapsulated in this vesicular particle. Regarding polypeptide-based component loading, and delivery potential of the niosome, some valuable studies have been conducted in recent years. However, exploring the full potential of this approach requires fine tuned optimization and characterization approaches. Therefore, this study was conducted to achieve the following two goals. First, formulation and optimization of bovine serum albumin (BSA) load and release behavior as a function of cholesterol (CH) to sorbitan monostearate (Span 60) molar ratio. Second, investigating a cost- and time-effective polypeptide detecting method via methyl orange (MO) dye. To this aim, BSA-loaded niosomes were prepared by reversed-phase evaporation technique. The effect of CH to Sorbitan monostearate (Span 60) molar ratio on noisome entrapment efficiency (EE%) and release profile of BSA was studied using a ultraviolet (UV) spectrophotometer technique (NanoDrop 2000/2000c).Niosome with a 60% CH content showed the highest BSA EE% and release behavior. Then, BSA was dyed using MO in an acidic solution and used in BSA-niosome formulation. The MO-colored protein, loaded into the vesicles, was successfully assessed by an inverted light microscope, in order to observe the protein location in the vesicle. The results obtained in this study can be useful for various applications in different fields, including pharmaceutical, cosmetics, and drug delivery in biomedical and tissue engineering.     

Poloxamer 407-based intranasal thermoreversible gel of zolmitriptan-loaded nanoethosomes: formulation,optimization, evaluation and permeation studies

Zolmitriptan is the drug of choice for migraine, but low oral bioavailability (<50%) and recurrence of migraine lead to frequent dosing and increase in associated side effects. Increase in the residence time of drug at the site of drug absorption along with direct nose to brain targeting of zolmitriptan can be a solution to the existing problems. Hence, in the present investigation, thermoreversible intranasal gel of zolmitriptan-loaded nanoethosomes was formulated by using mucoadhesive polymers to increase the residence of the drug into the nasal cavity. The preparation of ethosomes was optimized by using 3² factorial design for percent drug entrapment efficiency, vesicle size, zeta potential, and polydispersity index. Optimized formulation E6 showed the vesicle size (171.67?nm) and entrapment efficiency (66%) when compared with the other formulations. Thermoreversible gels prepared by using poloxamer 407 showed the phase transition temperature at 32–33?°C which was in line with the nasal physiological temperature. The optimized ethosomes were loaded into the thermoreversible mucoadhesive gel optimized by varying concentrations of poloxamer 407, carbopol 934, HPMC K100, and evaluated for gel strength, gelation temperature, mucoadhesive strength, in vitro drug release, and ex vivo drug permeation, where G3 and G6 were found to be optimized formulations. In vitro drug release was studied by different kinetic models suggested that G3 (n?=?0.582) and G6 (n?=?0.648) showed Korsemeyer–Peppas (K_KP) model indicating non-Fickian release profiles. A permeation coefficient of 5.92 and 5.9?µg/cm² for G3 and G6, respectively, revealed very little difference in release rate after 24?h between both the formulations. Non-toxic nature of the gels on columnar epithelial cells was confirmed by histopathological evaluation.     

Brain delivery of olanzapine by intranasal administration of transfersomal vesicles

The aim of this study was to investigate the presence of a possible direct correlation between vesicle elasticity and the amount of drug reaching the brain intranasally. Therefore, transfersomes were developed using phosphatidylcholine (PC) as the lipid matrix and sodium deoxycholate (SDC), Span^® 60, Cremophor^® EL, Brij^® 58, and Brij^® 72 as surfactants. The influence of the type of surfactant and PC-to-surfactant ratio on vesicle morphology, size, membrane elasticity, drug entrapment, and in vitro drug release was studied. The prepared transfersomes were mainly spherical in shape, with diameters ranging from 310 to 885?nm. Transfersomes containing SDC and Span 60 with optimum lipid-to-surfactant molar ratio showed suitable diameters (410 and 380?nm, respectively) and deformability indices (17.68 and 20.76?mL/sec, respectively). Values for absolute drug bioavailability in rat plasma for transfersomes containing SDC and those containing Span 60 were 24.75 and 51.35%, whereas AUC_0–360min values in rat brain were 22,334.6 and 36,486.3?ng/mL/min, respectively. The present study revealed that the deformability index is a parameter having a direct relation with the amount of the drug delivered to the brain by the nasal route.     

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.     

Nanoparticle-Based Topical Ophthalmic Gel Formulation for Sustained Release of Hydrocortisone Butyrate

This study was conducted to develop formulations of hydrocortisone butyrate (HB)-loaded poly(d,l-lactic-co-glycolic acid) nanoparticles (PLGA NP) suspended in thermosensitive gel to improve ocular bioavailability of HB for the treatment of bacterial corneal keratitis. PLGA NP with different surfactants such as polyvinyl alcohol (PVA), pluronic F-108, and chitosan were prepared using oil-in-water (O/W) emulsion evaporation technique. NP were characterized with respect to particle size, entrapment efficiency, polydispersity, drug loading, surface morphology, zeta potential, and crystallinity. In vitro release of HB from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when nanoparticles were suspended in thermosensitive gels and zero-order release kinetics was observed. In HCEC cell line, chitosan-emulsified NP showed the highest cellular uptake efficiency over PVA- and pluronic-emulsified NP (59.09?±?6.21%, 55.74?±?6.26%, and 62.54?±?3.30%, respectively) after 4 h. However, chitosan-emulsified NP indicated significant cytotoxicity of 200 and 500 μg/mL after 48 h, while PVA- and pluronic-emulsified NP exhibited no significant cytotoxicity. PLGA NP dispersed in thermosensitive gels can be considered as a promising drug delivery system for the treatment of anterior eye diseases.     

Diacerein niosomal gel for topical delivery: development,in vitro and in vivo assessment

The purpose of this study was to load diacerein (DCR) in niosomes by applying response surface methodology and incorporate these niosomes in gel base for topical delivery. Box–Behnken design was used to investigate the effect of charge-inducing agent (X₁), surfactant HLB (X₂) and sonication time (X₃) on the vesicle size (Y₁), entrapment efficiency (Y₂) and cumulative drug released (Y₃). DCR niosomal formulations were prepared by thin film hydration method. The optimized formula was incorporated in different gel bases. DCR niosomal gels were evaluated for homogeneity, rheological behavior; in vitro release and pharmacodynamic activity by carrageenan-induced hind paw edema method in the rat compared with DCR commercial gel. The results revealed that the mean vesicle sizes of the prepared niosomes ranged from 7.33 to 23.72?µm and the entrapment efficiency ranged from 9.52% to 58.43% with controlled release pattern over 8?h. DCR niosomal gels exhibited pseudoplastic flow with thixotropic behavior. The pharmacodynamic activity of DCR niosomal gel in 3% HPMC showed significant, 37.66%, maximum inhibition of edema size in comparison with 20.83% for the commercial gel (p?相似文献   

Enhanced transdermal delivery of salbutamol sulfate via ethosomes

The main objective of the present work was to compare the transdermal delivery of salbutamol sulfate (SS), a hydrophilic drug used as a bronchodilator, from ethosomes and classic liposomes containing different cholesterol and dicetylphosphate concentrations. All the systems were characterized for shape, particle size, and entrapment efficiency percentage, by image analysis optical microscopy or transmission electron microscopy, laser diffraction, and ultracentrifugation, respectively. In vitro drug permeation via a synthetic semipermeable membrane or skin from newborn mice was studied in Franz diffusion cells. The selected systems were incorporated into Pluronic F 127 gels and evaluated for both drug permeation and mice skin deposition. In all systems, the presence of spherical-shaped vesicles was predominant. The vesicle size was significantly decreased (P < .05) by decreasing cholesterol concentration and increasing dicetylphosphate and ethanol concentrations. The entrapment efficiency percentage was significantly increased (P < .05) by increasing cholesterol, dicetylphosphate, and ethanol concentrations. In vitro permeation studies of the prepared gels containing the selected vesicles showed that ethosomal systems were much more efficient at delivering SS into mice skin (in terms of quantity and depth) than were liposomes or aqueous or hydroalcoholic solutions.     

Niosome-Encapsulated Gentamicin for Ophthalmic Controlled Delivery

The objective of the present research was to investigate the feasibility of using non-ionic surfactant vesicles (niosomes) as carriers for the ophthalmic controlled delivery of a water soluble local antibiotic; gentamicin sulphate. Niosomal formulations were prepared using various surfactants (Tween 60, Tween 80 or Brij 35), in the presence of cholesterol and a negative charge inducer dicetyl phosphate (DCP) in different molar ratios and by employing a thin film hydration technique. The ability of these vesicles to entrap the studied drug was evaluated by determining the entrapment efficiency %EE after centrifugation and separation of the formed vesicles. Photomicroscopy and transmission electron microscopy as well as particle size analysis were used to study the formation, morphology and size of the drug loaded niosomes. Results showed a substantial change in the release rate and an alteration in the %EE of gentamicin sulphate from niosomal formulations upon varying type of surfactant, cholesterol content and presence or absence of DCP. In-vitro drug release results confirmed that niosomal formulations have exhibited a high retention of gentamicin sulphate inside the vesicles such that their in vitro release was slower compared to the drug solution. A preparation with 1:1:0.1 molar ratio of Tween 60, cholesterol and DCP gave the most advantageous entrapment (92.02% ± 1.43) and release results (Q_8h = 66.29% ± 1.33) as compared to other compositions. Ocular irritancy test performed on albino rabbits, showed no sign of irritation for all tested niosomal formulations.     

Investigating the penetrating potential of nanocomposite β-cycloethosomes: development using central composite design,in vitro and ex vivo characterization

Context: Atopic dermatitis (AD) is a chronic skin disease characterized by inflammation of the skin and has exhibited remarkable repercussions on human life across the globe. Fluocinolone acetonide (FA), a topical corticosteroid is employed in the treatment of atopic dermatitis, but suffers from limited penetration into deeper epidermis of atopic skin.

Objective: The present investigation was focused to explore the utility of β-cylcoethosomes in improvising the penetration deep into the skin.

Materials and methods: β-Cylcoethosomes developed using β-cycloamylose by injection method were evaluated for vesicle size, entrapment efficiency and in vitro release. Central Composite design employed for the preparation depicted FA8 as an optimized formulation which was then formulated as dermatological gel using carbomer 934P as a gel base. The gels were characterized for pH, viscosity, drug content and in vitro permeability.

Results and discussion: Optimized formulation (FA8) showed maximum desirability (0.795) with vesicle size of 228.33?±?1.23?nm), EE (82.49?±?1.21%) and CDR (90.90?±?0.29%). FA8-loaded gels showed maximum in vitro permeability as found in BG and BGP (83.22?±?0.72% and 84.02?±?0.87). BG was selected as an optimized gel and compared with optimized reference ethosomal gel and control gel. CLSM studies depicted deeper uniform penetration of fluorescent dye deep into the epidermis via BG. Improved penetration was observed due to the synergistic effect exerted by ethanol and β-cycloamylose.

Conclusion: β-cylcoethosomes proved to be a promising carrier for improvised penetration of fluocinolone acetonide via topical gel.     

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.     

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.     

Metformin hydrochloride and wound healing: from nanoformulation to pharmacological evaluation

Abstract

Niosomes as drug delivery systems have the ability to decrease drugs' side effects and increase their therapeutic effectiveness. Metformin HCl is an oral antihyperglycemic agent belonging to biguanides. It is the most commonly chosen drug as a startup therapy for patients newly diagnosed with type 2 diabetes. This study aims to encapsulate metformin HCl inside niosomes to be used as a transdermal formulation helping to prolong its antidiabetic effect and investigate its ability to enhance wound healing in diabetic patients. Thin film hydration method was used to prepare metformin HCl niosomes using different proportions of Span 60, Span 40, Tween 80, and cholesterol. All formulations were characterized using transmission electron microscope, zeta potential, and vesicle size. In vitro release studies, stability studies and in vivo evaluation were conducted on selected niosomal formulations. The results of entrapment efficiency ranged from 13% to 32%. Vesicle sizes were determined in nano-range. The in vitro release profile of metformin HCl from niosomes occurred in two consecutive phases. Biological evaluation on diabetic rats revealed that metformin HCl niosomal gel given every 2 days showed a better sustained antidiabetic effect than oral doses given daily. It also showed an improvement in wound healing for diabetic rats given metformin formulations compared to nontreated ones.     

Proniosomal Oral Tablets for Controlled Delivery and Enhanced Pharmacokinetic Properties of Acemetacin

Free-flowing proniosomal powders of acemetacin (AC) were prepared using the slurry method and maltodextrin as carrier. Positively charged proniosomes composed of 70:20:10 of Span 60/cholesterol (Chol)/stearylamine (SA), respectively, were successively compressed into tablets using direct compression method. The tablets were characterized for weight variability, friability, hardness, drug content uniformity, and dissolution properties. The in vivo evaluation of the prepared proniosomes (powder or tablet forms) after oral administration was investigated by the determination of AC and its active metabolite indomethacin (IND) in the blood of albino rabbits. Results indicated that the increase of Chol from 10% to 20% markedly reduced the efflux of the drug. Further Chol addition from 30% to 50% led to increased AC release rates. The proniosome tablets of AC showed greater hardness and disintegration time and less friability than AC plain tablets. The dissolution of proniosomal tablets indicated a lower drug release percentage compared to powdered proniosomes and AC plain tablets. The mean pharmacokinetic parameters of AC and IND from different formulations indicated increased t_1/2 and area under the curve (AUC) of both AC and IND for proniosomal tablets compared with both proniosomal powders and AC plain tablets. This study suggested the formulation of AC proniosomal powder into tablets to control and extend its pharmacologic effects.KEY WORDS: acemetacin, proniosomes, sustained-release tablet, pharmacokinetics     

Liposomes for (trans)dermal drug delivery: the skin-PVPA as a novel in vitro stratum corneum model in formulation development

Penetration potential of vesicles destined for trans(dermal) administration remains to be of great interests both in respect to drug therapy and cosmetic treatment. This study investigated the applicability of the phospholipid vesicle-based permeation assay (PVPA) as a novel in vitro skin barrier model for screening purposes in preformulation studies. Various classes of liposomes containing hydrophilic model drug were examined, including conventional liposomes (CLs), deformable liposomes (DLs) and propylene glycol liposomes (PGLs). The size, surface charge, membrane deformability and entrapment efficiency were found to be affected by the vesicle lipid concentration, the presence of the surfactant and propylene glycol. All liposomes exhibited prolonged drug release profiles with an initial burst effect followed by a slower release phase. The permeation of the drug from all of the tested liposomes, as assessed with the mimicked stratum corneum – PVPA model, was significantly enhanced as compared to the permeability of the drug in solution form. Although the DLs and the PGLs exhibited almost the same membrane elasticity, the permeability of the drug delivered by PGLs was higher (6.2?×?10^?6?cm/s) than DLs (5.5?×?10^?6?cm/s). Therefore, this study confirmed both the potential of liposomes as vesicles in trans(dermal) delivery and potential of the newly developed skin-PVPA for the screening and optimization of liposomes at the early preformulation stage.