Preparation and characterization of bioadhesive systems containing propolis or sildenafil for dental pulp protection

Purpose: Binary polymeric systems containing poloxamer 407 (P407) and Carbopol 934P (C934P) were designed to deliver propolis extract (PE) or sildenafil citrate for the endodontic treatment (pulp protection).

Methods: Gelation temperature, rheology (flow), bioadhesion, and in vitro drug release of formulations were determined.

Results: Formulations showed thermoresponsive behavior, existing as a liquid at room temperature and gel at 34–37°C. In addition, they exhibited pseudoplastic flow and low degrees of thixotropy or rheopexy. The greatest bioadhesion was noted in the formulation containing 20% P407 (w/w) and 0.10% C934P (w/w). PE release from formulation containing 15% P407 (w/w) and 0.25% C934P (w/w) was controlled by the phenomenon of relaxation of polymer chains. Moreover, sildenafil release from formulation containing 20% P407 (w/w) and 0.10% C934P (w/w) was controlled by Fickian diffusion.

Conclusion: The data obtained on these formulations indicate a potentially useful role in the endodontic treatment (pulp protection) and suggest they are worthy of clinical evaluation.     

Development of novel pH-sensitive nanoparticles loaded hydrogel for transdermal drug delivery

Objective: Difference of pH that exists between the skin surface and blood circulation can be exploited for transdermal delivery of drug molecules by loading drug into pH-sensitive polymer. Eudragit S100 (ES100), a pH-sensitive polymer having dissolution profile above pH 7.4, is used in oral, ocular, vaginal and topical delivery of drug molecules. However, pH-sensitive potential of this polymer has not been explored for transdermal delivery. The aim of this research work was to exploit the pH-sensitive potential of ES100 as a nanocarrier for transdermal delivery of model drug, that is, Piroxicam.

Methods: Simple nanoprecipitation technique was employed to prepare the nanoparticles and response surface quadratic model was applied to get an optimized formulation. The prepared nanoparticles were characterized and loaded into Carbopol 934 based hydrogel. In vitro release, ex vivo permeation and accelerated stability studies were carried out on the prepared formulation.

Results: Particles with an average size of 25–40?nm were obtained with an encapsulation efficiency of 88%. Release studies revealed that nanoparticles remained stable at acidic pH while sustained release with no initial burst effect was observed at pH 7.4 from the hydrogel. Permeation of these nanocarriers from hydrogel matrix showed significant permeation of Piroxicam through mice skin.

Conclusion: It can be concluded that ES100 based pH-sensitive nanoparticles have potential to be delivered through transdermal route.     

Rheological,mechanical, and bioadhesive behavior of hydrogels to optimize skin delivery systems

Background: Hydrogels are widely used for cutaneous formulations; thereby comparing the bioadhesive properties of polymers with a view to prolong the residence time of topical drugs on the skin would be very useful to design novel topical drug delivery systems.

Aim: The objective of this study was to correlate data from rheological studies and texture profile analysis, with bioadhesion on the skin.

Methods: Polyacrylic acid polymers used were carbomer homopolymer type A (C971) and type B (C974), and polycarbophil (PP) dispersed in water at various concentrations (0.1, 0.5, 1.0, 1.5, 2.0, 3.0, 5.0%, w/v). Rheological, texture, and bioadhesive properties were determined to compare the hydrogels.

Results: Rheological analysis showed that all samples exhibited pseudoplastic behavior with thixotropy. Texture profile analysis showed that compressibility, hardness, and adhesiveness of the hydrogels were dependent on the polymer concentration, and the cohesion values were high. Bioadhesion of C974 and PP at 0.5 and 2% was of the same magnitude, while all samples of C971 had lower values. The bioadhesion of 5% C974 was the highest, while that 5% PP was lower, possibly because PP showed the greatest hardness and this rigidity may decrease the interaction of the polymer with the skin.

Conclusion: A comprehensive comparative rheological and textural analyses of several polymers for topical systems were undertaken in terms of their bioadhesion. Therefore, it is possible to conclude that these polymers can be used for optimization of drug delivery systems on the skin.     

Development of topical hydrogels of terbinafine hydrochloride and evaluation of their antifungal activity

The purpose of this study was to prepare hydrogels and microemulsion (ME)-based gel formulations containing 1% terbinafine hydrochloride (TER-HCL) and to evaluate the use of these formulations for the antifungal treatment of fungal infections. Three different hydrogel formulations were prepared using chitosan, Carbopol® 974 and Natrosol® 250 polymers. A pseudo-ternary phase diagram was constructed, and starting from ME formulation, a ME gel form containing 1% Carbopol 974 was prepared. We also examined the characteristic properties of the prepared hyrogels. The physical stability of hydrogels and the ME -based gels were evaluated after storage at different temperatures for a period of 3 months. The release of TER-HCL from the gels and the commercial product (Lamisil®) was carried out by using a standard dialysis membrane in phosphate buffer (pH 5.2) at 32?°C. The results of the in vitro release study showed that the Natrosol gel released the highest amount of drug, followed by Carbopol gel, chitosan gel, commercial product, and the microoemulsion-based gel in that order. In vitro examination of antifungal activity revealed that all the prepared and commercial products were effective against Candida parapsilosis, Penicillium, Aspergillus niger and Microsporum. These results indicate that the Natrosol®-based hydrogel is a good candidate for the topical delivery of TER-HCL.     

Nanoethosomes for transdermal delivery of tropisetron HCl: multi-factorial predictive modeling,characterization, and ex vivo skin permeation

Objective: The aim of the present work is to exclusively optimize and model the effect of phospholipid type either egg phosphatidylcholine (EPC) or soybean phosphatidylcholine (SPC), together with other formulation variables, on the development of nano-ethosomal systems for transdermal delivery of a water-soluble antiemetic drug. Tropisetron HCl (TRO) is available as hard gelatin capsules and IV injections. The transdermal delivery of TRO is considered as a novel alternative route supposing to improve BAV as well as patient convenience.

Methods: TRO-loaded ethanolic vesicular systems were prepared by hot technique. The effect of formulation variables were optimized through a response surface methodology using 3?×?2²-level full factorial design. The concentrations of both PC (A) and ethanol (B) and PC type (C) were the factors, while entrapment efficiency (Y₁), vesicle size (Y₂), polydispersity index (Y₃), and zeta potential (Y₄) were the responses. The drug permeation across rat skin from selected formulae was studied. Particle morphology, drug–excipient interactions, and vesicle stability were also investigated.

Results: The results proved the critical role of all formulation variables on ethosomal characteristics. The suggested models for all responses showed good predictability. Only the concentration of phospholipid, irrespective to PC type, had a significant effect on the transdermal flux (p?Conclusion: The study suggests the applicability of statistical modeling as a promising tool for prediction of ethosomal characteristics. The ethanolic vesicles were considered as novel potential nanocarriers for accentuated transdermal TRO delivery.     

Effect of Aging on the Bioavailability of Nitrdfurantoin Tablets Containing Carbopol 934

Abstract

This article reports a study of two nitrofurantoin tablet formulations differing in the percentage of Carbopol 934 used as binder. The tablets of both formulations each contained 50 mg of nitrofurantoin. Those of formulation A contained 0.625 mg of Carbopol 934, and those of formulation B 1.25 mg. When freshly prepared, tablets of both formulations were bioequivalent to capsules containing 50 mg of nitrofurantoin, but a year's storage at 40°C and 60% relative humidity caused a significant decrease in the bioavailability of nitrofurantoin from formulation B, whereas formulation A was still bioequivalent to capsules. USP XXI Ed. Method II successfully reflected the observed variations in bioavailability, but not Method I.     

Intradermal and follicular delivery of adapalene liposomes

Abstract

Background: Adapalene is a widely used topical anti-acne drug; however, it has many side effects. Liposomal drug delivery can play a major role by targeting delivery to pilosebaceous units, reducing side effects and offering better patient compliance.

Objective: To prepare and evaluate adapalene-encapsulated liposomes for their physiochemical and skin permeation properties.

Methods: A liposomal formulation of adapalene was prepared by the film hydration method and characterized for shape, size, polydispersity index (PDI), encapsulation efficiency and thermal behavior by techniques such as Zetasizer®, differential scanning calorimetry and transmission electron microscopy. Stability of the liposomes was evaluated for three months at different storage conditions. In vitro skin permeation studies and confocal laser microscopy were performed to evaluate adapalene permeation in pig ear skin and hair follicles.

Results: The optimized process and formulation parameters resulted in homogeneous population of liposomes with a diameter of 86.66?±?3.5?nm in diameter and encapsulation efficiency of 97.01?±?1.84% w/w. In vitro permeation studies indicated liposomal formulation delivered more drug (6.72?±?0.83?μg/cm²) in hair follicles than gel (3.33?±?0.26?μg/cm²) and drug solution (1.62?±?0.054?μg/cm²). Drug concentration delivered to the skin layers was also enhanced compared to other two formulations. Confocal microscopy images confirmed drug penetration in the hair follicles when delivered using the liposomal formulation.

Conclusion: Adapalene was efficiently encapsulated in liposomes and led to enhanced delivery in hair follicles, the desired target site for acne.     

Preparation and evaluation of floating tablets of pregabalin

Abstract

Floating tablets of pregabalin were prepared using different concentrations of the gums (xanthan gum and guar gum), Carbopol 974P NF and HPMC K100. Optimized formulations were studied for physical tests, floating time, swelling behavior, in vitro release studies and stability studies. In vitro drug release was higher for tablet batches containing guar and xanthan gum as compared to the batches containing Carbopol 974P NF. Tablet batches were subjected to stability studies and evaluated by different parameters (drug release, drug content, FTIR and DSC studies). The optimized tablet batch was selected for in vivo pharmacodynamic studies (PTZ induced seizures). The results obtained showed that the onset of jerks and clonus were delayed and extensor phase was abolished with time in treated groups. A significant difference (p?>?0.05) was observed in control and treated group behavior indicating an excellent activity of the formulation for a longer period (>12?h).     

Elastic liposomes-in-vehicle formulations destined for skin therapy: the synergy between type of liposomes and vehicle

Objective: The present study is focused on optimization of elastic liposomes-in-vehicle formulations in respect to drug release and formulation properties. By combining penetration potential of elastic liposomes containing high ratio of entrapped drug and physicochemical properties of vehicles, both affecting the release and texture properties, optimal formulation could be achieved.

Materials and methods: Deformable, propylene glycol-containing or conventional liposomes with hydrophilic model drug (diclofenac sodium) were incorporated into the following vehicles appropriate for skin application: a hydrogel, a cream base and derma membrane structure base cream (DMS base). Each formulation was assessed for in vitro drug release and mechanical properties.

Results and discussion: The composition and type of both liposomes and the vehicle affected the rate and amount of the released drug. The cream base exhibited the slowest release, followed by the hydrogel and DMS base. Similar release profiles were achieved with both types of elastic vesicles (deformable and propylene glycol liposomes); the slowest release was observed for conventional liposomes, regardless of the vehicle used. The drug release profiles from different liposomes-in-vehicle formulations were in agreement with the physicochemical properties of the formulations. All of the liposomes were found to be compatible with the hydrogel preserving its original textures, whereas a significant decrease in all texture parameters was observed for liposomes-in-DMS base, regardless of liposome type.

Conclusion: Propylene glycol liposomes-in-hydrogel is considered as the optimal formulation for improving skin delivery of hydrophilic drug. Further investigations involving in vivo animal studies are necessary to confirm its applicability in skin therapy.     

Increased absorption of mangiferin in the gastrointestinal tract and its mechanism of action by absorption enhancers in rats

The therapeutic efficiency of mangiferin is restricted by its low intestinal permeability. In order to improve the oral absorption of mangiferin, potential of enhancers, including TPGS, sodium deoxycholate and Carbopol 974P, were investigated in a series of in vivo experiments. After administration of mangiferin at a dose of 30?mg/kg combining with sodium deoxycholate, the bioavailability of mangiferin increased four-fold, and this may be due to sodium deoxycholate weakening the compactness between lecithin molecules and increased the paracellular permeability. When Carbopol 974P (100?mg/kg) was combined with mangiferin, the oral bioavailability of it increased seven-fold compared with the control group, and this may be related to the mucoadhesive properties of Carbopol 974P and paracellular drug permeation. However, following coadministration of TPGS (50?mg/kg), the oral absorption of mangiferin increased slightly compared with that of the control group (p > 0.05). The increased oral absorption by the three coexcipients was in the order of Carbopol 974P > sodium deoxycholate > TPGS. The absolute bioavailability of mangiferin in the three different doses following oral administration were evaluated based on the AUC_(0–t) of the intravenous dose and there was no increase from low doses to high doses (25?mg/kg to 100?mg/kg). The above results show that the low absorption of mangiferin was due to presence of a narrow absorption window, which may also exist in these compounds, which have structures similar to mangiferin including three fused aromatic rings with polyphenolic hydroxyl groups. Bioadhesion polymers are effective enhancers of the absorption of mangiferin in the gastrointestinal tract.     

Release of Tolmetin from Carbomw Gel Systems

Abstract

Gel-formulations containing a nonsteroidal anti-inflammatory drug, tolmetin, were prepared using three different carbomers namely, Carbopol? 934, 940 and 941. Effects of cosolvent composition, carbomer type, carbomer concentration and drug concentration on drug release from the gels were analyzed by factorial design. Gels with high aqueous content yielded significantly higher tolmetin release rates than gels with lower aqueous content. Although no significant differences in drug release characteristics were observed between the three carbomer gels, there was a trend in the release profiles; fastest drug release was observed from Carbopol? 941 gels and the slowest drug release was observed from Carbopol? 940 gels. Increasing the carbomer concentration from 1% w/w to 2% w/w had no significant effect on drug release from gel formulations prepared with all the three different types of carbomers. However, increasing the tolmetin concentration in the gels from 1% w/w to 4% w/w resulted in a dramatic increase in drug release. An investigation of the mechanism of drug release from the gels revealed that tolmetin release was diffusion controlled, except at the outset.     

Design and in vitro characterization of buccoadhesive tablets of timolol maleate

Objective: The purpose of this work was to develop and evaluate buccoadhesive tablets of timolol maleate (TM) due to its potential to circumvent the first-pass metabolism and to improve its bioavailability.

Methods: The tablets were prepared by direct compression using two release modifying polymers, Carbopol 974P (Cp-974p) and sodium alginate (SA). A 3² full factorial design was employed to study the effect of independent variables, Cp-974p and SA, in various proportions in percent w/w, which influences the in vitro drug release and bioadhesive strengths. Physicochemical properties of the drug were evaluated by ultraviolet, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffraction (P-XRD). Tablets were evaluated for hardness, thickness, weight variation, drug content, surface pH, swelling index, bioadhesive force and in vitro drug release.

Results: The FTIR and DSC studies showed no evidence of interactions between drug, polymers and excipients. The P-XRD study revealed that crystallinity of TM remain unchanged in optimized formulation tablet. Formulation F9 achieves an in vitro drug release of 98.967%?±?0.28 at 8?h and a bioadhesive force of 0.088 N?±?0.01211.

Conclusion: We successfully developed buccal tablet formulations of TM and describe a non-Fickian-type anomalous transport as the release mechanism.     

Preparation and irradiation of Pluronic F127-based thermoreversible and mucoadhesive hydrogel for local delivery of naproxen

To improve physical properties and modulate the mucoadhesive hydrogel formulation via cross-linking by radiation, hydrogels were prepared using thermoreversible polymer Pluronic F127 (PF127) and mucoadhesive polymer carbopol 934P (C934P). As a model drug, naproxen was loaded in the hydrogel formulation. Sol-gel transition temperatures of hydrogels were measured by the tube-inversion method. The mucoadhesive potential of each formulation was determined by measuring the force required to detach the formulation from oral mucosal tissue. To strengthen the mechanical properties, the formulations were irradiated using an electronic beam. Drug release from the hydrogels and the cytotoxicity of each formulation were investigated. Sol-gel transition temperatures of the formulations were decreased by the addition of carbopol and were close to body temperature. The mucoadhesive force of the PF127 formulation was increased by addition of carbopol. In vitro release was sustained and the release rate was reduced by the addition of carbopol. After irradiation, the mucoadhesive force was increased about five-fold especially in the case of PF127 23% (9.7 kPa) and in vitro release was not sustained further. In conclusion, the use of a PF127 formulation incorporating a mucoadhesive polymer could effectively and safely improve oral residence time and absorption of naproxen. Irradiated formulations showed permanent cross-linking and improved properties.     

In vitro models to estimate drug penetration through the compromised stratum corneum barrier

Objectives: The phospholipid vesicle-based permeation assay (PVPA) is a recently established in vitro stratum corneum model to estimate the permeability of intact and healthy skin. The aim here was to further evolve this model to mimic the stratum corneum in a compromised skin barrier by reducing the barrier functions in a controlled manner. Methods: To mimic compromised skin barriers, PVPA barriers were prepared with explicitly defined reduced barrier function and compared with literature data from both human and animal skin with compromised barrier properties. Caffeine, diclofenac sodium, chloramphenicol and the hydrophilic marker calcein were tested to compare the PVPA models with established models. Results and discussions: The established PVPA models mimicking the stratum corneum in healthy skin showed good correlation with biological barriers by ranking drugs similar to those ranked by the pig ear skin model and were comparable to literature data on permeation through healthy human skin. The PVPA models provided reproducible and consistent results with a distinction between the barriers mimicking compromised and healthy skin. The trends in increasing drug permeation with an increasing degree of compromised barriers for the model drugs were similar to the literature data from other in vivo and in vitro models. Conclusions: The PVPA models have the potential to provide permeation predictions when investigating drugs or cosmeceuticals intended for various compromised skin conditions and can thus possibly reduce the time and cost of testing as well as the use of animal testing in the early development of drug candidates, drugs and cosmeceuticals.     

Effect of vehicle systems, pH and enhancers on the permeation of highly lipophilic aripiprazole from Carbopol 971P gel systems across human cadaver skin

The objective of this study was to investigate the effect of vehicle systems, pH and enhancers on the permeation of a highly lipophilic basic drug aripiprazole (ARPZ) through human cadaver skin. Solubility of ARPZ in single, binary, tertiary, and quaternary vehicle systems of N-methyl pyrrolidone (NMP), dimethyl sulfoxide (DMSO), water, ethanol and isopropyl myristate (IPM) was studied. Gel formulations of 5% ARPZ were developed with 0.5% Carbopol 971P in quaternary vehicle systems consisting of NMP, DMSO, water and ethanol or IPM at optimum ratio of 40/40/5/15. The effect of pH of the gel formulations and fatty acids with different chain lengths on the permeation was studied. The flux of ARPZ from gel formulation with IPM and ethanol was comparable. A four fold increase in APRZ flux was observed when the pH of the gel systems was lowered from pH 8.2 to pH 6 or pH 7. For fatty acids, the order of flux is lauric acid > myristic acid > caprylic acid > oleic acid. In all the cases, in vitro permeation rate of ARPZ through human cadaver skin followed zero order kinetics. This study demonstrated that ARPZ in tertiary vehicle system of NMP/DMSO/water/IPM at ratio of 40/40/5/15 and gel system of Carbopol 971P with pH 7 is a promising candidate for transdermal delivery.     

Hydrogel containing adapalene- and dapsone-loaded lipid-core nanocapsules for cutaneous application: development,characterization, in vitro irritation and permeation studies

Lipid-core polymeric nanocapsule suspensions containing adapalene and dapsone (AD-LCNC) were developed and incorporated in a Carbopol 940® hydrogel (AD-LCNC HG). A nanoemulsion (AD-NE), similarly prepared but omitting the polymer, was developed and also incorporated in a Carbopol 940^® hydrogel (AD-NE HG) to evaluate the polymer effect. Physicochemical characteristics were evaluated. AD-LCNC suspensions containing 0.07% of dapsone and 0.025% of adapalene presented an average size of 194.9?±?0.42?nm, zeta potential of ?15?±?1.2?mV and polydispersity index of 0.12?±?0.02, using electrophoretic light scattering (n?=?3). The granulometric profiles showed unimodal size distributions for AD-LCNC suspensions, demonstrating that no microscopic population is present in the formulation. No instability phenomena were observed by multiple light-scattering analysis. Photomicrographs obtained by TEM showed homogeneous- and spherical-shaped particles. The encapsulation efficiency was 99.99% for dapsone and 100% for adapalene. The pH values for AD-LCNC suspensions were 5.1 and 7.6 for AD-LCNC HG. Formulations were classified as nonirritant in the HET-CAM test. Rheological analysis demonstrated a non-Newtonian pseudoplastic profile. The in vitro skin permeation studies showed a higher amount of adapalene in epidermis (130.52?±?25.72?ng/mg) and dermis (4.66?±?2.5?ng/mg) for AD-NE HG. The AD-LCNC HG presented higher amount of dapsone in both the skin layers (73.91?±?21.64?ng/mg in epidermis and 4.08?±?0.85?ng/mg in dermis). The assay showed significant difference between AD-LCNC HG and AD-NE HG (p?相似文献   

Bioadhesive Polymers - Synthesis,Evaluation and Application in Controlled Release Tablets

Abstract

Synthesis of series of cross linked polymers of methacrylic acid (PMAs) and acrylic acid (PAAs) is reported. Polymers of both the types have been investigated for physiochemical properties like solubility, density, swelling index and equilibrium swelling. A suitable method was devised for study of bioadhesion. Floating tablets were prepared and coated with some of the synthesized polymers. The tablets were then evaluated for physical properties (including bioadhesion) as well as for drug content and in vitro drug release. The results were compared with those obtained with Carbopol 934P. Some polymers showed better bioadhesion and drug release pattern as compared to Carbopol 934P.     

Design and optimization of thermosensitive nanoemulsion hydrogel for sustained-release of praziquantel

Objective: This work aimed to develop an alternative sustained-release thermosensitive praziquantel-loaded nanoemulsion (PZQ-NE) hydrogel for better schistosomiasis treatment.

Significance: PZQ-NE-dispersed chitosan/glycerol 2-phosphate disodium/HPMC (NE/CS/β-GP/HMPC) hydrogel was successfully prepared to improve bioavailability of PZQ.

Methods: Solubility tests and pseudo-ternary phase diagrams were applied to screen optimal oils, surfactants and co-surfactants of NE. The hydrogels were characterized for gelling time, surface exudates, rheological properties and in vitro drug release. Formulation optimization of NE/CS/β-GP/HMPC hydrogel was conducted by Box–Behnken experimental design combined with response surface methodology. In vitro cytotoxicity of hydrogel was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide method. The sustained-release property of PZQ in NE and optimized hydrogel was evaluated by pharmacokinetic study in rabbits.

Results: The formulation of PZQ-NE consisted of mass ratio of 12.5% capryol 90 containing PZQ (160?mg/g), 40% cremophor RH 40/tween 20 and transcutol HP (S/CoS?=?2:1), 47.5% deionized water. PZQ releasing from NE/CS/β-GP/HMPC hydrogels was best fitted to Higuchi model and governed by diffusion. Rheological investigation evidenced the themosensitive gelation of different hydrogel systems and their gel-like character at 37?°C. The optimized hydrogel formulation consisted of HPMC solution (103.69?mg/g), 3.03% (w/v) chitosan and 14.1% (w/v) β-GP showed no cytotoxicity when the addition of NE was no more than 100?mg/g. Pharmacokinetic parameters indicated that NE/CS/β-GP/HMPC hydrogel can significantly slow down drug elimination, prolong mean residence time and improve bioavailability of PZQ.

Conclusions: NE/CS/β-GP/HMPC hydrogel possessed sustained-release property and could be an alternative antischistosomal drug delivery system with improved therapeutic effect.     

Development of hydrogels,oleogels, and bigels as local drug delivery systems for periodontitis

Periodontal disease is a chronic inflammation of gum and tissues that surround and support the teeth. Nonsteroidal anti-inflammatory drugs (NSAIDs) can be used in the treatment of periodontitis to ease swelling and inflammation. One approach of treating periodontitis is loading the NSAIDs in local drug delivery systems. Therefore, the objective of this study was to investigate the local delivery of the NSAIDs model drug ibuprofen to treat periodontitis using different types of gel formulations (hydrogel, oleogel, and bigel). Gel formulations were characterized in terms of their rheological properties (flow behavior, viscoelastic, and bioadhesive properties) using a controlled-stress rheometer. The in vitro drug release of ibuprofen from gel formulations was investigated using Franz diffusion cells. Gels exhibited more solid-like (elastic) behavior. The viscosity and viscoelastic properties were in the order of oleogel?>?bigel?>?hydrogel, respectively. In bioadhesion study, mucin dispersion/plain ibuprofen-hydrogel mixture showed a frequency-dependent interaction of ΔG’?=??31 and ΔG’?=?+?53?Pa at 1 and 10?rad/s, respectively. A strong positive interaction (ΔG’?=?+?6000 and +130,667?Pa at 1 and 10?rad/s, respectively) was found in mucin dispersion/plain ibuprofen–oleogel mixture. The extent of the negative interaction increased in mucin dispersion/plain ibuprofen-bigel mixture (ΔG’?=??59,000 and ?79,375?Pa at 1 and 10?rad/s, respectively). After 6?h, ibuprofen release from hydrogel, oleogel, and bigel was 59.5?±?2.2, 80.6?±?3.9, and 94.6?±?3.2%, respectively. Results showed that the rheological and bioadhesive properties and in vitro drug release were influenced by the type of gel formulations.     

Development,optimization, and characterization of a novel tea tree oil nanogel using response surface methodology

Purpose: To develop and optimize nanoemulsion (NE)-based emulgel (EG) formulation as a potential vehicle for topical delivery of tea tree oil (TTO).

Methodology: Central composite design was adopted for optimizing the processing conditions for NE preparation by high energy emulsification method viz. surfactant concentration, co-surfactant concentration, and stirring speed. The optimized NE was developed into emulgel (EG) using pH sensitive polymer Carbopol 940 and triethanolamine as alkalizer. The prepared EG was evaluated for its pH, viscosity, and texture parameters, ex vivo permeation at 37?°C and stability. Antimicrobial evaluation of EG in comparison to conventional gel and pure TTO was also carried out against selected microbial strains.

Results and discussion: Optimized NE had particle size and zeta potential of 16.23?±?0.411?nm and 36.11?±?1.234?mV, respectively. TEM analysis revealed the spherical shape of droplets. The pH of EG (5.57?±?0.05?) was found to be in accordance with the range of human skin pH. EG also illustrated efficient permeation (79.58?μL/cm²) and flux value (J_SS) of 7.96?μL cm²/h through skin in 10?h. Viscosity and texture parameters, firmness (9.3?±?0.08?g), spreadability (2.26?±?0.06?mJ), extrudability (61.6?±?0.05?mJ), and adhesiveness (8.66?±?0.08?g) depict its suitability for topical application. Antimicrobial evaluation of EG with same amount of TTO as conventional gel revealed broader zones of growth inhibitions against all the selected microbial strains. Moreover, EG was also found to be nonirritant (PII 0.0833). These parameters were consistent over 90 d.

Conclusion: TTO EG turned out to be a promising vehicle for the topical delivery of TTO with enhanced therapeutic efficacy.