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.     

Design and evaluation of proniosomes as a carrier for ocular delivery of lomefloxacin HCl

The current investigation aims to develop and evaluate novel ocular proniosomal gels of lomefloxacin HCl (LXN); in order to improve its ocular bioavailability for the management of bacterial conjunctivitis. Proniosomes were prepared using different types of nonionic surfactants solely and as mixtures with Span 60. The formed gels were characterized for entrapment efficiency, vesicle size, and in vitro drug release. Only Span 60 was able to form stable LXN-proniosomal gel when used individually while the other surfactants formed gels only in combination with Span 60 at different ratios. The optimum proniosomal gel; P-LXN 7 (Span 60:Tween 60, 9:1) appeared as spherical shaped vesicles having high entrapment efficiency (>80%), appropriate vesicle size (187?nm) as well as controlled drug release over 12?h. Differential scanning calorimetry confirmed the amorphous nature of LXN within the vesicles. Stability study did not show any significant changes in entrapment efficiency or vesicle size after storage for 3 months at 4?°C. P-LXN 7 was found to be safe and suitable for ocular delivery as proven by the irritancy test. The antibacterial activity of P-LXN 7 evaluated using the susceptibility test and topical therapy of induced ocular conjunctivitis confirmed the enhanced antibacterial therapeutic efficacy of the LXN-proniosomal gel compared to the commercially available LXN eye drops.     

Solid lipid nanoparticles for transdermal delivery of avanafil: optimization,formulation, in-vitro and ex-vivo studies

Context: Avanafil (AVA) is used in the treatment of erectile dysfunction, but is reported for its poor aqueous solubility. Solid lipid nanoparticles (SLNs) are lipid carriers that can greatly enhance drug solubility and bioavailability.

Objective: This work was aimed to formulate and optimize AVA SLNs with subsequent loading into hydrogel films for AVA transdermal delivery.

Materials and methods: AVA SLNs were prepared utilizing homogenization followed by ultra-sonication technique. The prepared SLNs were characterized for particle size, charge, surface morphology and drug content. The optimized SLNs formulation was incorporated into transdermal films prepared using HPMC and chitosan. Hydrogel films were evaluated for ex-vivo rat skin permeation using automated Franz diffusion cells. The permeation parameters and the release mechanism were evaluated. The transdermal permeation of the prepared AVA SLNs through the skin layers was studied using confocal laser scanning microscope.

Results: Lipid concentration and % of oil in lipid had a pronounced effect on particle size while, entrapment efficiency was significantly affected by lipid concentration and % of cholesterol. The optimized AVA SLNs showed particle size and entrapment efficiency of 86?nm and 85.01%, respectively. TEM images revealed spherecity of the particles. High permeation parameters were observed from HPMC films loaded with AVA SLNs. The release data were in favor of Higuchi diffusion model. The prepared AVA SLNs were able to penetrate deeper in skin layers.

Conclusion: HPMC transdermal film-loaded AVA SLNs is an effective and alternative to per-oral drug administration.     

Effect of polyamidoamine (PAMAM) dendrimers on the in vitro release of water-insoluble nifedipine from aqueous gels

The objective of this study was to determine the effect of ethylenediamine core PAMAM dendrimers, on the release of nifedipine suspended in aqueous gels and to correlate release to the increase in solubility afforded by the dendrimers. Drug release from aqueous 5% HPMC gels containing nifedipine (2% wt/vol) through 0.2-μm membranes was measured using Enhancer cells and 50% ethanolic solution as the receptor medium. The release from gels containing PAMAM G-3 and G-5 (0.25%–1% wt/vol) was compared with gels containing the cosolvent isopropyl alcohol (10%–80% vol/vol). PAMAM dendrimers significantly increased the solubility of nifedipine. This caused a significant increase in the release rate of nifedipine from the gel suspensions. The increase in drug release depended on the concentration and generation size of the dendrimers added. For higher generations (G-5) lower concentrations were needed to obtain equivalent increases in release. Although the increase in solubility and release was not as high as from gels containing high concentrations of the cosolvent isopropyl alcohol, the dendrimers prevented the recrystallization of the drug that was observed when the gels containing isopropyl alcohol were left open. Published: October 24, 2005     

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.     

Influence of Critical Parameters of Nanosuspension Formulation on the Permeability of a Poorly Soluble Drug through the Skin—A Case Study

In transdermal drug delivery systems, it is always a challenge to achieve stable and prolonged high permeation rates across the skin since the concentrations of the drug dissolved in the matrix have to be high in order to maintain zero order release kinetics. Several attempts have been reported to improve the permeability of poorly soluble drug compounds using supersaturated systems. However, due to thermodynamic challenges, there was a high tendency for the drug to nucleate immediately after formulating or even during storage. The present study focuses on the efficiency of nanoparticles and influence of different concentrations of solubilizer such as vitamin E TPGS (d-a-tocopheryl polyethylene glycol 1000 succinate) to improve the permeation rate through the skin. Effects of several formulation factors were studied on the nanosuspension systems using ibuprofen as a model drug. The overall permeation enhancement process through the skin was influenced mostly by the solubilizer and also by the size of nanoparticles. The gel formulation developed with vitamin E TPGS + HPMC nanosuspension, consequently represent a promising approach aiming to improve the permeability performance of a poorly water soluble drug candidate.KEY WORDS: dermal drug delivery, human skin, nanosuspension, permeation rate, porcine skin, vitamin E TPGS     

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     

Preparation and Evaluation of Diltiazem Hydrochloride Diffusion-Controlled Transdermal Delivery System

The objective was to investigate the suitable polymeric films for the development of diltiazem hydrochloride (diltiazem HCl) transdermal drug delivery systems. Hydroxypropyl methylcellulose (HPMC) and ethylcellulose (EC) were used as hydrophilic and hydrophobic film formers, respectively. Effects of HPMC/EC ratios and plasticizers on mechanical properties of free films were studied. Effects of HPMC/EC ratios on moisture uptake, in vitro release and permeation through pig ear skin of diltiazem HCl films were evaluated. Influence of enhancers including isopropyl myristate (IPM), isopropyl palmitate (IPP), N-methyl-2-pyrrolidone, oleic acid, polyethylene glycol 400, propylene glycol, and Tween80 on permeation was evaluated. It was found that addition of EC into HPMC film produced lower ultimate tensile strength, percent elongation at break and Young’s modulus, however, addition of EC up to 60% resulted in too hard film. Plasticization with dibutyl phthalate (DBP) produced higher strength but lower elongation as compared to triethyl citrate. The moisture uptake and initial release rates (0–1 h) of diltiazem HCl films decreased with increasing the EC ratio. Diltiazem HCl films (10:0, 8:2 and 6:4 HPMC/EC) were studied for permeation because of the higher release rate. The 10:0 and 8:2 HPMC/EC films showed the comparable permeation-time profiles, and had higher flux values and shorter lag time as compared to 6:4 HPMC/EC film. Addition of IPM, IPP or Tween80 could enhance the fluxes for approx. three times while Tween80 also shorten the lag time. In conclusion, the film composed of 8:2 HPMC/EC, 30% DBP and 10% IPM, IPP or Tween80 loaded with 25% diltiazem HCl should be selected for manufacturing transdermal patch by using a suitable adhesive layer and backing membrane. Further in vitro permeation and in vivo performance studies are required.     

Guar Gum,Xanthan Gum,and HPMC Can Define Release Mechanisms and Sustain Release of Propranolol Hydrochloride

The objectives were to characterize propranolol hydrochloride-loaded matrix tablets using guar gum, xanthan gum, and hydroxypropylmethylcellulose (HPMC) as rate-retarding polymers. Tablets were prepared by wet granulation using these polymers alone and in combination, and physical properties of the granules and tablets were studied. Drug release was evaluated in simulated gastric and intestinal media. Rugged tablets with appropriate physical properties were obtained. Empirical and semi-empirical models were fit to release data to elucidate release mechanisms. Guar gum alone was unable to control drug release until a 1:3 drug/gum ratio, where the release pattern matched a Higuchi profile. Matrix tablets incorporating HPMC provided near zero-order release over 12 h and erosion was a contributing mechanism. Combinations of HPMC with guar or xanthan gum resulted in a Higuchi release profile, revealing the dominance of the high viscosity gel formed by HPMC. As the single rate-retarding polymer, xanthan gum retarded release over 24 h and the Higuchi model best fit the data. When mixed with guar gum, at 10% or 20% xanthan levels, xanthan gum was unable to control release. However, tablets containing 30% guar gum and 30% xanthan gum behaved as if xanthan gum was the sole rate-retarding gum and drug was released by Fickian diffusion. Release profiles from certain tablets match 12-h literature profiles and the 24-h profile of Inderal^® LA. The results confirm that guar gum, xanthan gum, and HPMC can be used for the successful preparation of sustained release oral propranolol hydrochoride tablets.     

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.     

<Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Evaluation of Proniosomes Containing Celecoxib for Oral Administration

The objectives of this research were to prepare celecoxib proniosomes and evaluate the influence of proniosomal formulation on the oral bioavailability of the drug in human volunteers. A new proniosomal delivery system for a poorly water-soluble drug such as celecoxib was developed and subjected to in vitro and in vivo studies. Proniosomes were prepared by sequential spraying method, which consisted of cholesterol, span 60, and dicetyl phosphate in a molar ratio of 1:1: 0.1, respectively. The average entrapment percent of celecoxib proniosome-derived niosomes was about 95%. The prepared proniosomes showed marked enhancement in the dissolution of celecoxib as compared to pure drug powder. The bioavailability of 200 mg single dose of both celecoxib proniosomal formulation and a conventional marketed celecoxib capsule was studied in human volunteers. The obtained results show that the proniosomal formulation significantly improved the extent of celecoxib absorption than conventional capsule. The mean relative bioavailability of the proniosomal formulation to the conventional capsule was 172.06 ± 0.14%. The mean T _max for celecoxib was prolonged when given as proniosomal capsule. There was no significant difference between the values of K _el and t _1/2 for both celecoxib preparations. In conclusion, the proniosomal oral delivery system of celecoxib with improved bioavailability was established.     

Formulation of Niosomal Gel for Enhanced Transdermal Lopinavir Delivery and Its Comparative Evaluation with Ethosomal Gel

The aim was to develop niosomal gel as a transdermal nanocarrier for improved systemic availability of lopinavir. Niosomes were prepared using thin-film hydration method and optimized for molar quantities of Span 40 and cholesterol to impart desirable characteristics. Comparative evaluation with ethosomes was performed using ex vivo skin permeation, fluorescence microscopy, and histopathology studies. Clinical utility via transdermal route was acknowledged using in vivo bioavailability study in male Wistar rats. The niosomal formulation containing lopinavir, Span 40, and cholesterol in a molar ratio of 1:0.9:0.6 possessed optimally high percentage of drug entrapment with minimum mean vesicular diameter. Ex vivo skin permeation studies of lopinavir as well as fluorescent probe coumarin revealed a better deposition of ethosomal carriers but a better release with niosomal carriers. Histopathological studies indicated the better safety profile of niosomes over ethosomes. In vivo bioavailability study in male Wistar rats showed a significantly higher extent of absorption (AUC_0→∞, 72.87 h × μg/ml) of lopinavir via transdermally applied niosomal gel as compared with its oral suspension. Taken together, these findings suggested that niosomal gel holds a great potential of being utilized as novel, nanosized drug delivery vehicle for transdermal lopinavir delivery.KEY WORDS: ethosomes, lopinavir, niosomes, transdermal     

Formulation development and in vitro and in vivo evaluation of membrane-moderated transdermal systems of ampicillin sodium in ethanol: pH 4.7 buffer solvent system

The objective of the present study was to develop membrane-moderated transdermal systems of ampicillin sodium and to evaluate them with respect to various in vitro and in vivo parameters. The membrane-type transdermal systems were prepared using a drug with various antinucleant polymers— hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), cellulose acetate phthalate, chitosan, sodium alginate (SA), and sodium carboxymethylcellulose—in an ethanol: pH 4.7 buffer volatile system by the solvent evaporation technique with HPMC as the rate-controlling membrane for all the systems. The swelling properties of the polymers were studied, and drug-polymer interaction studies were performed. The patches were subjected to various physicochemical studies, in vitro release studies, permeation studies, and skin irritation studies. The best patch among the formulations was selected for further in vivo studies. Compared to the other patches, SA exhibited the highest moisture content at 16%; a 21% moisture uptake was found with MC. The release and permeation of the drug from the SA patch was found to be the maximum. The in vivo study of the SA patch exhibited a peak plasma concentration C_max of 126 μg/mL at T_max 4 hours. Hence, it can be concluded that hydrophilic ampicillin sodium can be developed as a transdermal delivery system with SA that is an alternative to intravenous administration and has minimal adverse effects. Published: January 26, 2007     

The Experimental Evaluation and Molecular Dynamics Simulation of a Heat-Enhanced Transdermal Delivery System

Transdermal delivery systems are useful in cases where preferred routes such as the oral route are not available. However, low overall extent of delivery is seen due to the permeation barrier posed by the skin. Chemical penetration enhancers and invasive methods that disturb the structural barrier function of the skin can be used to improve transdermal drug delivery. However, for suitable drugs, a fast-releasing transdermal delivery system can be produced by incorporating a heating source into a transdermal patch. In this study, a molecular dynamics simulation showed that heat increased the diffusivity of the drug molecules, resulting in faster release from gels containing ketoprofen, diclofenac sodium, and lidocaine HCl. Simulations were confirmed by in vitro drug release studies through lipophilic membranes. These correlations could expand the application of heated transdermal delivery systems for use as fast-release-dosage forms.     

Comparative Study to Investigate the Effect of Meloxicam or Minocycline HCl In Situ Gel System on Local Treatment of Periodontal Pockets

In situ gelling formulations allow easy application to the target area. Gelation is induced by physiological stimuli at the site of application where the formula attains semisolid properties and exerts sustained drug release. In situ gelling formulations containing either 3% meloxicam (Mx) or 2% minocycline HCl (MH) were prepared for local application into the periodontal pockets. Gel formulations were based on the thermosensitive Pluronic^® (Pl) and the pH-sensitive Carbopol^® (C) polymers. C gels were prepared in combination with HPMC (H) to decrease its acidity. The total percent drug released from Pl formulae was 21.72% after 1 week for Mx and 85% after 3 days for MH. Their release kinetics data indicated anomalous non-Fickian behavior that could be controlled by both diffusion and chain relaxation. Addition of MH to C/H gels (1:2.5) resulted in liquefaction, followed by drug precipitation. Regarding C/H gel containing Mx, it showed a prolonged release rate up to 7 days with an initial burst effect; the kinetics data revealed Fickian-diffusion mechanism. The in vitro antibacterial activity studies for MH gel in Pl revealed that the drug released exceeded the minimum inhibitory concentration (MIC) of MH against Staphylococcus aureus ATCC 6538; placebo gel showed no effect on the microorganism. Clinical evaluation of Pl gels containing either Mx or MH showed significant improvement in chronic periodontitis patients, manifested by decrease in pocket depth and gingival index and increase in bone density.     

Development and Evaluation of Ethyl Cellulose-Based Transdermal Films of Furosemide for Improved In Vitro Skin Permeation

Transdermal films of the furosemide were developed employing ethyl cellulose and hydroxypropyl methylcellulose as film formers. The effect of binary mixture of polymers and penetration enhancers on physicochemical parameters including thickness, moisture content, moisture uptake, drug content, drug–polymer interaction, and in vitro permeation was evaluated. In vitro permeation study was conducted using human cadaver skin as penetration barrier in modified Keshary–Chein diffusion cell. In vitro skin permeation study showed that binary mixture, ethyl cellulose (EC)/hydroxypropyl methylcellulose (HPMC), at 8.5:1.5 ratio provided highest flux and also penetration enhancers further enhanced the permeation of drug, while propylene glycol showing higher enhancing effect compared to dimethyl sulfoxide and isopropyl myristate. Different kinetic models, used to interpret the release kinetics and mechanism, indicated that release from all formulations followed apparent zero-order kinetics and non-Fickian diffusion transport except formulation without HPMC which followed Fickian diffusion transport. Stability studies conducted as per International Conference on Harmonization guidelines did not show any degradation of drug. Based on the above observations, it can be reasonably concluded that blend of EC–HPMC polymers and propylene glycol are better suited for the development of transdermal delivery system of furosemide.     

Development and evaluation of topical formulation containing solid lipid nanoparticles of vitamin A

The purpose of this research was to investigate novel particulate carrier system such as solid lipid nanoparticles (SLN) for topical application of vitamin A palmitate and to study its beneficial effects on skin. Topical gels enriched with SLN of vitamin A were prepared. The solid lipid nanoparticulate dispersion was prepared using high-pressure homogenization technique and was incorporated into polymeric gels of Carbopol, Pemulen, Lutrol, and Xanthan gum for convenient application. The nanoparticulate dispersion and its gels were evaluated for various parameters such as particle size, in vitro drug release, in vitro penetration, in vivo skin hydration, and skin irritation. The solid lipid nanoparticulate dispersion showed mean particle size of 350 nm. Differential scanning calorimetry studies revealed no drugexcipient incompatibility. In vitro release profile of vitamin A palmitate from nanoparticulate dispersion and its gel showed prolonged drug release up to 24 hours, which could be owing to embedment of drug in the solid lipid core. In vitro penetration studies showed almost 2 times higher drug concentration in the skin with lipid nanoparticle-enriched gel as compared with conventional gel, thus indicating better localization of the drug in the skin. In vivo skin hydration studies in albino rats revealed increase in the thickness of the stratum corneum with improved skin hydration. The developed formulation was nonirritant to the skin with no erythema or edema and had primary irritation index of 0.00. Thus it can be concluded that SLN represents a promising particulate carrier having controlled drug release, improved skin hydration, and potential to localize the drug in the skin with no skin irritation.     

Swelling behavior and controlled release of theophylline and sulfamethoxazole drugs in beta-lactoglobulin protein gels obtained by phase separation in water/ethanol mixture

Physically cross-linked beta-lactoglobulin (BLG) protein gels containing theophylline and sulfamethoxazole low molecular weight drugs were prepared in 50% ethanol solution at pH 8 and two protein concentrations (6 and 7% (w/v)). Swelling behavior of cylindrical gels showed that, irrespective of the hydrated or dehydrated state of the gel, the rate of swelling was the highest in water. When the gels were exposed to water, they first showed a swelling phase in which their weight increased 3 and 30 times for hydrated and dehydrated gels, respectively, due to absorption of water, followed by a dissolution phase. The absorption of solvent was however considerably reduced when the gels were exposed to aqueous buffer solutions. The release behavior of both theophylline and sulfamethoxazole drugs from BLG gels was achieved in a time window ranging from 6 to 24 h. The drug release depended mainly on the solubility of the drugs and the physical state of the gel (hydrated or dry form). Analysis of drug release profiles using the model of Peppas showed that diffusion through hydrated gels was governed by a Fickian process whereas diffusion through dehydrated gels was governed partly by the swelling capacities of the gel but also by the structural rearrangements inside the network occurring during dehydration step. By a judicious selection of protein concentration, hydrated or dehydrated gel state, drug release may be modulated to be engineered suitable for pharmaceutical as well as cosmetics and food applications.     

Design and <Emphasis Type="Italic">In Vitro</Emphasis> Evaluation of Capsaicin Transdermal Controlled Release Cubic Phase Gels

The purpose of this study was to design and investigate the transdermal controlled release cubic phase gels containing capsaicin using glycerol monooleate (MO), propylene glycol (1,2-propanediol, PG), and water. Three types of cubic phase gels were designed based on the ternary phase diagram of the MO–PG–water system, and their internal structures were confirmed by polarizing light microscopy (PLM) and small-angle X-ray scattering (SAXS). Release results showed the cubic phase gels could provide a sustained system for capsaicin, while the initial water content in the gels was the major factor affecting the release rate. Release kinetics was determined to fit Higuchi’s square-root equation indicating that the release was under diffusion control. The calculated diffusion exponent showed the release from cubic phase gels was anomalous transport. The unique structure of the cubic phases, capsaicin distributed in the lipid bilayers, and cubic phase gel swelling contributed to the release mechanism. The cubic phase gel may be an interesting application for transdermal delivery system of capsaicin in alleviating the post-incision pain.