Mucoadhesive Gel Research Articles

Preparation and characterization of mucoadhesive gels containing pentoxifylline loaded nanoparticles for vaginal delivery of genital ulcer

Mucoadhesive gel formulations containing pentoxifylline (PTX)-loaded nanoparticle (NP) for the treatment of genital ulcer were prepared and evaluated. In that context, formulation properties like particle size (PS), polydispersity index (PI), zeta potential (ZP), drug content and entrapment efficiency (EE), rheology, mucoadhesion, swelling index, in vitro drug release, cytotoxicity, radio-labeling, and cell binding were evaluated. The prepared NP formulation exhibited a small PS with a narrow distribution, a high ZP and a high EE. In addition, the mucoadhesive gel formulation showed a non-Newtonian plastic flow, good mucoadhesive properties, a suitable swelling index, represented as water absorption and retention abilities, a burst release within the first 1 h and release of more than 95% during the first 8 h, no cytotoxicity on PCS-480-010™ cells and a high cell binding rate of radio-labeled formulation. Mucoadhesive gel formulation containing PTX-loaded NP is beneficial for enhancing the therapeutic efficacy of PTX administered through vaginal route by increasing the retention time and the easiness for local application in the vaginal mucosa. The prepared formulation is a promising candidate for vaginal application of PTX, which could be further investigated with in vivo animal studies.

Current Status of Mucoadhesive Gel Systems for Buccal Drug Delivery.

Buccal drug delivery is a fascinating research field. Gel-based formulations present potent characteristics as buccal systems since they have great physicochemical properties. Among the various gels, in situ gels are viscous colloidal systems consisting of polymers; when physiological conditions change (pH, temperature, ion activation), they are transformed into the gel phase. These systems can improve bioavailability. Other systems, such as nanogels or emulgels can also be applied for buccal delivery with promising results. Polymeric gel-based systems can be produced by natural, semisynthetic, and synthetic polymers. Their main advantage is that the active molecules can be released in a sustained and controllable manner. Several gels based on chitosan are produced for the entrapment of drugs demonstrating efficient retention time and bioavailability due to chitosan mucoadhesion. Besides polysaccharides, poloxamers and carbopol are also used in buccal gels due to their high swelling ability and reversed thermal gelation behavior. Herein, the authors focused on the current development of mucoadhesive gel systems used in buccal drug delivery. After explaining buccal drug delivery and mucoadhesion, various studies with hydrogels, in situ gels, and nanogels were analyzed as buccal gel systems. Various mucoadhesive gel studies with mucoadhesive polymers have been studied and summarized. This review is presented as valuable guidance to scientists in formulating buccal mucoadhesive drug delivery systems. This review aimed to assist researchers working on buccal drug delivery by summarizing buccal drug delivery, mucoadhesion, and buccal mucoadhesive gel systems recently found in the literature.

A novel approach for the treatment of oral ulcerative lesion using mucoadhesive proniosome gel

A mucoadhesive proniosome gel containing a potent corticosteroid drug (fluticasone propionate) was formulated for the local treatment of oral ulcerative lesions. The formula was made-up in an attempt to avoid the drug's severe systemic adverse effects, moreover, ensuring both efficacy and safety. Full factorial design was employed to prove the significant effect of surfactant type and cholesterol concentration on entrapment efficiency and vesicle size of the formulated proniosome gels. The optimum formula with an entrapment efficiency of 85.5 ± 2.4% was incorporated into mucoadhesive gels using different mucoadhesive polymers, namely, xanthan gum or sodium alginate. The effects of the polymer type and its concentration on the quantity of fluticasone propionate release as well as on the mucoadhesion force were studied. The optimum formula was found to possess a mucoadhesion force of 14425 ± 5.4 dyne/cm2 and maximum quantity of drug release of 89 ± 0.09% which showed to follow Higuchi diffusion model of release. High-resolution transmission electron micrographs revealed that the chosen formula was smooth, homogenous and in nano size range. Cytotoxicity assay test was conducted to ensure the safety of the optimum formula. Curing of oral ulcerative lesions using an animal model was assessed and emphasized by the histopathological findings.

Tailored Doxycycline Hyclate Loaded In Situ Gel for the Treatment of Periodontitis: Optimization, In Vitro Characterization, and Antimicrobial Studies.

Currently, periodontitis is treated by oral dosage forms (antibiotics) which shows systemic side effects and failed to reach the therapeutic concentration (above minimum inhibitory concentration, MIC) in the periodontal pocket. The present study aimed to overcome the above issues, by designing tailored doxycycline hyclate laden in situ gel by Poloxamer 407, chitosan, and polyethylene glycol 600. The in situ gel-forming system has attracted attention owing to its ability of sustained drug release above MIC, easy administration (syringeability), and high drug retention (localization) in the periodontal cavity. The Box-Behnken design (BBD) was used to tailor and optimize the concentration of Poloxamer 407 (X1 = 14.3%), chitosan (X2 = 0.58%), and polyethylene glycol 600 (X3 = 1.14%) to achieve sufficient syringeability (149 N), t90% (1105 min), and viscosity at non-physiological condition (512 cps) and physiological condition (5415 cps). The optimized in situ gel was clear and isotonic (RBCs test). The gelation temperature of the optimized in situ was 34 ± 1°C with sufficient mucoadhesive strength (26 ± 2 dyn/cm2), gel strength (29 ± 2 sec), and texture profile for periodontal application. The in vitro drug release studies showed sustain release from optimized in situ gel (24h) in comparison to marketed gel (7h). The antimicrobial activity (cup plate technique) of the in situ gel was equivalent to the marketed doxycycline gel, which suggests that the doxycycline hyclate retained its antimicrobial efficacy when formulated as in situ gelling system. In conclusion, BBD was effectively utilized to optimize in situ gel with minimum level of polymers to achieve the required characteristics of the in situ gel for sustaining drug delivery to treat periodontitis.

In vitro evaluation of mucoadhesive in situ nanogel of celecoxib for buccal delivery

The research aims for finding the possibility of buccal delivery of celecoxib from an in situ mucoadhesive nanogel, and in vitro evaluation of the gel to evidence the enhanced permeation of drug from buccal mucosa. Six formulations of celecoxib loaded NLCs were prepared using stearic acid and oleic acid in different ratio in aqueous solution of poloxamer by emulsion solvent evaporation technique. The physicochemical evaluations of the celecoxib loaded NLC (CeL-NLC) were carried out. The formulation F4 was selected as the best and subjected for FTIR, DSC, PXRD, and surface morphology study. In situ mucoadhesive gel was prepared with F4 in HPC, HPMC and Carbopol 934 gelling systems. The gels were evaluated for their mechanical and rheological properties and in vitro permeation studies through rabbit oral mucosa. The selected process at high shear homogenization could yield nanoparticles of desired physiochemical properties. The drug and excipients were compatible as disseminated from FTIR study. Transformation of the crystal form to amorphous form of celecoxib was revealed by the solid-state characterization studies. The AFM study unfold the formation of discrete asymmetric nano particles. All mucoadhesive gels found to have good mucoadhesion and rheological property with good in vitro permeation of drug. A comparative study and statistical analysis unveiled that gel containing Carbopol 934 was found to be the best mucoadhesive in situ gel of nano particles of celecoxib with enhanced permeation parameters. Therefore, the above in vitro evaluation of in situ mucoadhesive nano gel proved the potential of the formulation as a promising buccal delivery of celecoxib.

Design and evaluation of mucoadhesive in situ liposomal gel for sustained ocular delivery of travoprost using two steps factorial design

Travoprost (TRAVO) is a prostaglandin analog used to reduce the intraocular pressure (IOP) for patients suffering from glaucoma and ocular hypertension. The aim of the present study was the development of a novel in situ mucoadhesive ocular liposomal gel to prolong and improve therapeutic efficacy of TRAVO. With this purpose, liposomal formulations were prepared by implementing a full factorial design to study the effect of three factors; type of permeation enhancer (PE), PE concentration and the ratio of lecithin: cholesterol at two levels. The evaluated responses were entrapment efficiency (EE), vesicle size (VS), polydispersibility (PDI) and zeta potential (ZP). L6 (selected liposomal formulation), composed of 20% sodium deoxycholate (Na DOC) and lecithin: cholesterol at 4:1 ratio showed high EE (67.55%), suitable Ps and PDI (74.19 nm and 0.433) and ZP (−75.5 mv). L6 was incorporated in a second 31 × 21 design to study the effect of concentration of gellan gum (at three level) and carbopol 934 (at two levels) to develop in situ mucoadhesive gel. Selected liposomal in situ gel LISG2 (0.25% gellan gum and 0.5% carbopol 934), showed minimum release (18.2%) after 30 min and maximum release after 24 h (72.5%) and achieve maximum viscosity (4445cps) at physiological conditions, mucoadhesive force (0.438 N), with minimum viscosity (124 cps) at normal conditions. Selected LISG2 will be further in vivo evaluated for irritation and pharmacokinetic. TRAVO LISG was non irritant and showed improved bioavailability (higher concentration of TRAVO in aqueous humor) when compared to the marketed product, and showed more prolonged effect compared to liposomal formulation.

Development of rasagiline mesylate loaded solid lipid nanoparticles in a thermosensitive mucoadhesive gel: Formulation design using DoE, in-vitro and ex-vivo characterization

Development of rasagiline mesylate loaded solid lipid nanoparticles in a thermosensitive mucoadhesive gel: Formulation design using DoE, in-vitro and ex-vivo characterization

Preparation and Evaluation of Physicochemical Properties of the Doxepin Mucoadhesive Gel

Background: Oral mucositis is a common debilitating complication of cancer chemotherapy and radiotherapy that can reduce the quality of patient’s lives. Hence, treating this condition plays an important role in increasing the patient’s tolerance. Objectives: Doxepin mucoadhesive gel is useful for treating oral mucosa inflammation caused by long-term effects of chemotherapy, which has low adverse effects. Methods: Doxepin gel’s formulation was prepared with various concentrations of poloxamer 407 and hydroxypropyl methylcellulose in deionized water. The prepared gels were evaluated for pH, appearance, viscosity, spreadability, stability, and drug release. Results: After providing gels containing doxepin, formulations 1, 2, 8, and 9 had low quality and, thus, were removed from the study. Based on qualitative evaluations, formulations 3 and 4 did not meet the criteria for mucoadhesive gel and were removed from the study. The best formulation contained 17% w/w poloxamer 407, 10% w/w hydroxypropyl methylcellulose, and 5% w/w doxepin. Conclusions: Suitable physicochemical properties of prepared doxepin mucoadhesive gel enable it to well cover inflamed and damaged oral mucosa. On the other hand, doxepin’s slow release from formulation (8 hours) can increase therapeutic effects and reduce side effects, which can heal and soothe inflammations of the oral mucosa and be useful in cancer patient’s treatment.

Natural polymers for vaginal mucoadhesive delivery of vinegar, using design of experiment methods

Background/Aim. Vinegar is one of the main international traditional nutraceuticals, and it has been used as a vaginal health protectant due to vagina pH balance maintenance and antimicrobial properties. Since the main form of vinegar is liquid, it is difficult to apply vaginally due to its short retention. The aim of this study was to design a vaginal mucoadhesive gel made of vinegar. Methods. Xanthan gum and tragacanth were utilized as natural gel-forming polymers. The effects of xanthan gum and tragacanth on mucoadhesion strength and drug release of the gel formulations were optimized using a 3 level (32) factorial design. Several physico-chemical properties of the gel formulations, including gel viscosity, lubricity, scanning electron microscopy (SEM) images of hydrogel chains, and chain release kinetic, were also investigated. Results. It was found that tragacanth possessed a statistically significant effect on release rate control (p-value = 0.0027), while both tragacanth and xanthan gum had a significant effect (p-value = 0.0001 and 0.0017, respectively) on mucoadhesion property. Formulation F7 with 5% xanthan gum and 1% tragacanth (mucoadhesion = 0.4632 N and re-lease rate = 88.8% in 6 hours) considered as the optimum formulation with some modifications. Conclusion. Xanthan gum and tragacanth can be considered as appropriate natural polymers for vaginal drug delivery.

Development and Characterization of Mucoadhesive Buccal Gel Containing Lipid Nanoparticles of Triamcinolone Acetonide

Abstract: Background: Triamcinolone Acetonide is a synthetic glucocorticosteroid which has been used for its immunosuppressive and anti-inflammatory activity belonging to BCS class IV, yet it is not recommended to be used at higher doses due to its possible adverse effects. Lipid nanoparticle systems are good carriers for poor water soluble drugs, improve permeability and show sustained drug release. Materials and Methods: Triamcinolone Actinide was formulated as Nanostructured Lipid Carriers. High shear homogenization followed by ultra-sonication method was used with Precirol ATO 5 and Isopropyl myristate as lipids. Optimisation was based on their particle size and entrapment efficiency using the design expert software. Conclusion:Formulations F-5 and F-7 were selected as optimised formulations and had drug release patterns that fit Korsmeyer-peppas model kinetics. SEM and TEM studies showed that the Nano structured lipid carriers had size within the nanometre range and morphology resembling type II (amorphous type). The mucoadhesive gel of optimised formulations F-5 and F-7 were prepared as a 1% w/w hydrogel with carbopol 934. These gels showed pseudoplastic fluid nature and good physical properties and also showed a more sustained drug release in comparison to gel incorporated drug suspension. Conclusion: Based on the results obtained it was concluded that Triamcinolone Actinide can be successfully formulated as a gel incorporated with Nanostructured lipid carriers for treatment of buccal diseases. Key words: Triamcinolone Acetonide, Nanostructured lipid carriers, Mucoadhesive buccal gel, Factorial Design, Response Surface plot.

PHARMACOLOGICAL STUDIES OF THE DENTAL GEL OF COMBINED COMPOSITION

The growing prevalence of periodontal and oral mucosa diseases results in increasing number of people in need of orthopedic treatment due to tooth loss, which, accordingly, requires quality dental care.
 The aim – is to study the pharmacological action of a new dental drug of combined composition in the form of a mucoadhesive gel under the conditional name "Cholident" for the treatment and prevention of inflammatory diseases of the periodontium, oral mucosa and to facilitate adaptation to removable dentures.
 Material and Methods. The study of antiexudative activity of the dental gel was performed on a model of carrageenan edema using electronic plethysmometer, manufactured by WPI. As a reference drug, "Kamistad®" gel (STADA Arzneimittel, AG, Germany) was used. Evaluation of the reparative effect of the gel was performed on the model of thermal burn. At light optical research of histologic micronutrients epithelialization, border zone creation, infiltration of inflammatory cells (macrophages) and angiogenesis have been evaluated.
 Results. After application of the gel under study, the antiexudative effect began to appear after 30 minutes, as evidenced by a decrease in the volume of the affected paw, while a similar effect of the comparison drug was observed only 60 minutes after application to the paw. The study drug also showed a longer action, as the antiexudative effect was still observed 120 min after application, while in the control group there was no decrease in paw volume after 90 min of the experiment. Sustained decrease of the combustion wound area in the animals to which the studied gel was applied has been demonstrated. Activation of epithelial proliferation in the border area, increase in the height of regenerating epidermis and formation of a thin layer of cells in the combustion area, signs of demarcation zone formation, and increase in density of newly formed vessels in the border zone dermis have been revealed by the results of histological examination.
 Conclusions. The results show that the studied gel has a moderate anti-inflammatory effect, which in severity and duration of action exceeds the comparison drug, reduces the local inflammatory response and promotes skin regeneration in the acute phase of combustion.

Recent Developments and Potential of Mucoadhesive Buccal Drug Delivery System for Oro-mucosal Disorders

Background: The drug delivery across buccal mucosa is a very interesting option for the treatment of various oro-mucosal disorders such as aphthous stomatitis, periodontitis, gingivitis, toothache, periodontitis, and sjorgensen syndrome. But it is quite difficult because of target site movements, limited area for drug absorption, drinking of fluids, intake of food and saliva flow at regular intervals, contributing to poor retention and sub-therapeutic level of drug at the target site. Due to this, the mucoadhesive buccal drug delivery system has gained a great deal of attention among the various scientists and researchers over the last two decades. Methods: Mucoadhesion is a process of attachment between the natural or synthetic macromolecule and mucosal epithelial surface with the aid of interfacial attractive forces. The process of mucoadhesion has been extensively encouraged by the utilization of mucoadhesive polymers within the formulation that on contact with salivary fluid swells and adheres to buccal epithelium membrane, thus prolonging the drug release, retention time and improving therapeutic performance in case of oral diseases. The present review tries to cover the basic anatomy and structure of oral mucosa, pathways of drug absorption, the theory of mucoadhesion, mechanisms involved in mucoadhesion and various factors affecting mucoadhesion. Results: It highlights the properties of mucoadhesive polymers in drug delivery along with various dosage forms such as mucoadhesive tablets, films, patches, gels, and pastes. Furthermore, it also sheds light on the recent developments made in the field of mucoadhesive buccal drug delivery system that reflects the potential of this system for the effective treatment of oro-mucosal disorders. Conclusion: It can be concluded that the mucoadhesive buccal drug delivery system has great potential in the near future for treating oro-mucosal disorders.

Nose-to-Brain Delivery of Diazepam from an Intranasal Aqua-Triggered In-Situ (ATIS) Gelling Microemulsion: Monitoring Brain Uptake by Microdialysis.

An innovative intranasal aqua-triggered in-situ (ATIS) gel is a polymer-free in-situ gelling microemulsion which gels instantaneously on contact with minute quantities of water to form a mucoadhesive gel. The objective of the study was to develop ATIS diazepam (ATIS-diazepam) as an alternative to the injection for epileptic emergencies and evaluate its brain uptake and nose-to-brain targeting efficiency in rats. ATIS-diazepam (1mg/100 µL) was prepared and characterized for in vitro formulation characteristics. An LC-MS/MS method was developed and validated for the bioanalysis of diazepam. In vivo studies for pharmacokinetics, brain uptake and nasal irritation of intranasal ATIS-diazepam were conducted in rats. Brain uptake was investigated with brain microdialysis, a highly sensitive technique enabling quantification of free drug, which correlates to efficacy. ATIS-diazepam exhibited globule size < 200nm, low viscosity, negative zeta potential and good stability. A significant increase in mucoadhesion was exhibited by ATIS-diazepam following the addition of a small quantity of water. ATIS-diazepam showed burst release in pH 6.4 with 50% diazepam release in ~ 10min, which was sustained over 1h. The absolute bioavailability was ~ 50% with both intranasal free-diazepam and ATIS-diazepam. Intranasal administration of ATIS-diazepam revealed immediate absorption with rapid and high brain extracellular fluid concentration compared to intravenous free-diazepam solution. The estimated direct transport potential and drug targeting efficiency of intranasal ATIS-diazepam was significantly higher (2-fold) than intranasal free-diazepam solution, which was attributed to the mucoadhesive and microemulsion properties of ATIS-diazepam. The nasal irritation study revealed the safety of ATIS-diazepam compared to free-diazepam solution. Intranasal ATIS-diazepam showed promise of higher direct nose-to-brain targeting, better safety and hence has an immense implication in the treatment of epileptic emergencies.

Mucoadhesive Ionic Liquid Gel Patches for Oral Delivery.

Oral delivery of biologic drugs is a highly desired yet challenging goal because of the many barriers posed by the GI tract. Ionic liquids (ILs) and deep eutectic solvents (DESs) such as choline and geranate (CAGE) have demonstrated the potential to improve intestinal absorption of insulin and poorly soluble drugs. As with other delivery agents, localization of the ILs in the intestine can enhance the delivery potential by increasing local concentrations while maintaining low off-target concentrations, thus improving the therapeutic window of the ILs. Here, we describe a method of encapsulating CAGE into a gel using PVA, forming a mucoadhesive ionogel patch (CAGE-patch) designed to adhere to the intestine. CAGE-patches formed via repeated freeze-thaw cycles demonstrated mucoadhesive strength, swelling, and controlled release of both CAGE and insulin. In vitro transport studies revealed a more than 30% increase in insulin transport when compared to controls across Caco-2 and HT29-MTX-E12 coculture layers. This design provides a novel approach to localize ionic liquids and therapeutics in the GI tract for enhanced oral delivery.

Thiolated PVP-Amphotericin B Complexes: An Innovative Approach toward Highly Mucoadhesive Gels for Mucosal Leishmaniasis Treatment.

The aim of this study was to synthesize polymeric excipients that can form mucoadhesive hydrogels containing amphotericin B (AmB) for the treatment of mucosal leishmaniasis. 2-(2-Acryloylaminoethyldisulfanyl)-nicotinic acid (ACENA) was copolymerized with N-vinyl pyrrolidone to obtain thiolated polyvinylpyrrolidone (PVP) that was then complexed with AmB to improve its solubility. The resulting structure of thiolated PVP was evaluated by 1H nuclear magnetic resonance to confirm S-protected thiol groups, and the average molecular mass was determined by size exclusion chromatography. Moreover, variants of thiolated PVP-AmB were studied for the thiol content, amount of complexed AmB, cytotoxicity, mucoadhesive properties, and antileishmaniasis activity. The highest achieved degree of thiolation was 772 ± 24.64 μmol/g, and the amount of complexed AmB was 27.05 ± 0.31 μmol per g of polymer. Thiolated PVP and thiolated PVP-AmB variants (0.5% m/v) showed no cytotoxicity, whereas the equivalent concentration of free AmB reduced Caco-2 cell viability to 70% within 24 h. Thiol-functionalized PVP and PVP-AmB complexes displayed 7.66- and 7.20-fold higher adhesion to the mucosal surface in comparison to unmodified PVP and PVP-AmB, respectively. In addition, variants of thiolated PVP-AmB complexes displayed 100% antileishmaniasis activity in comparison to the 80% killing efficiency of Fungizone, which has been applied in the equivalent AmB concentration of 0.2 μg/mL. Thiol-functionalized PVP proved to be a promising novel excipient for the delivery of AmB providing enhanced solubility and improved mucoadhesive properties which are beneficial for the treatment of mucosal leishmaniasis.

Amino Functionalized Micro-Mesoporous Hybrid Particles for the Sustained Release of the Antiretroviral Drug Tenofovir.

The sustained release of an antiretroviral agent to women mucosa has been proved as an excellent strategy to reduce the sexual transmission of HIV. Hybrid micro-mesoporous particles have been synthesized and functionalized with a silane coupling agent followed by loading the antiretroviral tenofovir. It has been observed that the disposition of the silane molecule on the surface of the particles determines the interaction mechanism with the antiretroviral molecule loaded independently on the surface area of the particles. In this sense, available and free amino groups are required to achieve a smart pH-responsive material, a condition that is only achieved in those materials containing a silane chemisorbed monolayer. Moreover, the modulation of the release kinetics attributed to the presence of the silane monolayer covering the mesopores has been confirmed by fitting the releasing curves to the first order and Weibull models. The developed micro-mesoporous particles have been demonstrated to be excellent smart-release vehicles for antiviral agents and can be safely used in polymer mucoadhesive vaginal gels.

DISCLOSING AGENT FROM RED DRAGON FRUIT PEEL AS DENTAL PLAQUE INDICATOR

Background: Red dragon fruit peel mucoadhesive gel has the potential to dye dental plaque. The colour of a transparent dental plaque can be seen with visualize using dyes (disclosing agent). One of the natural products containing dyestuff betacyanin, namely the peel of the red dragon (Hylocereus polyrhizus). This research aimed to review the peels of red dragon betacyanin (Hylocereus polyrhizus) in the mucoadhesive gel formula as an alternative disclosing agent. Method: Research is done with the manufacture of thick peels of a red dragon extract with the maceration methods. In clinical trials carried out an application red dragon fruit peel mucoadhesive gel 10%, concentration 15 % and Three-Tone Plaque Disclosing Gel. The assessment of plaque was carried out using the O’leary method. Result: The results obtained were analyzed by the t-test method. The mean of plaque index scores with red dragon fruit peel mucoadhesive gel concentrations of 10% (22.08), 15% (26,29) and Three-Tone Plaque Disclosing Gel (66,21; 64,20). The effectiveness of the gel with a concentration of 10% is 33.87%, and 15% concentration is 40.32%. Conclusion: The mucoadhesive gel of red dragon fruit peel has the potential to colour dental plaque.

Formulation and Characterization of Cinnarizine Targeted Aural Transfersomal Gel for Vertigo Treatment: A Pharmacokinetic Study on Rabbits.

Introduction and AimCinnarizine is indicated orally for treating vertigo associated with Ménière’s syndrome and has a local anesthetic effect as well. The present study aims to develop an aural Cinnarizine mucoadhesive transfersomal gel to overcome the first-pass metabolism.MethodsEighteen Cinnarizine transfersomes were prepared by the thin-film hydration technique using different types of phosphatidylcholine and edge activators in different ratios. Formulae were tested for their appearance, entrapment efficiency, and in-vitro drug release after eight hours. F1, F4, F7, F9, F10, and F12 were selected to be examined for particle size, polydispersity index, and zeta potential. According to the previous parameters, F1 and F10 were incorporated into gels using different polymers according to factorial design 23. The eight gels were tested for appearance, pH, mucoadhesion, spreadability, drug content, in-vitro drug release after eight hours, and rheology. The transfersomal gel F1A was subjected to FTIR analysis and in-vivo pharmacokinetic study.ResultsThe transfersomal dispersion colors were ranging between the white and yellow. Their EE % ranged from 64.36±1.985% to 94.09±1.74%, and their in-vitro release percentages were between 61.82±1.92% and 95.92±1.18%. Also, the vesicles PS ranged from 212.3±30.05nm to 2150±35.35nm, DI from 0.238±0.134 to 1±0.00 and zeta potential from −57.5±2.54 to +4.73±1.57 mV. The transfersomal gels showed pseudoplastic behavior, pH range of 5.5 to 8, a mucoadhesive force of 169.188±1.26 to 321.212±6.94 (dyne/cm2×102), spreadability of 40 ±7.03mm to 138 ±3.77mm, and in-vitro drug release of 81.63±1.128% to 97.78±0.102%. The IR spectra of the (drug-excipients) physical mixture revealed that there were no shifts of incompatibility. The in-vivo pharmacokinetic study illustrated that [AUC]0–24 of F1A was significantly higher than that of tablets at (P< 0.05), equivalent to 703.563±26.470 and 494.256±9.621ɲg.hr/mL respectively.ConclusionThe study revealed that Cinnarizine aural mucoadhesive targeted delivery provides an improved systemic bioavailability over the conventional oral route.

Development of Clove Oil &lt;i&gt;In Situ&lt;/i&gt; Gels for Buccal Mucoadhesive

Clove oil is the volatile essential oil obtained from Syzygium aromaticum. Eugenol, which is the main component, has antimicrobial, antifungal activity and antioxidant. From antiseptic activity, clove oil can be used in treatment of oral cavity infection. The aims of this research are to formulate and evaluate clove oil mucoadhesive gel for oral applications. Gel bases were prepared from Poloxamer 407 (P407). The effect of clove oil, P407 and xanthan gum on formulations were studied. Clove oil preparations were evaluated for their physicochemical properties (physical appearance, pH, viscosity, gelling capacity and gel dissolving time at 37 °C in artificial saliva). Mucoadhesive property was studied using porcine buccal mucosa. The amount of eugenol in clove oil was analyzed by gas chromatography (GC). Stability study of clove oil gel was performed under stress and room temperature conditions (1 month). The results showed that preparations containing 0% and 1% clove oil were in situ gel while those containing 3% and 5% clove oil were gel. All formulations showed good and clear physical appearance with the pH value of 5.2. The gelling capacity and gel dissolving time of more than 15 minutes in artificial saliva at 37°C was found in all preparations. They also showed mucoadhesive property. The GC results showed that the amount of eugenol in clove oil were 99.52 ± 0.51 %V/V. The preparations containing 1% clove oil showed good physical and chemical stability after storage at room temperature for 1 month. There was no significant difference in the amount of eugenol after storage (p&gt;0.05). In conclusion, the preparations containing 20% P407 and 1% clove oil are the most appropriate formulation.

OCULAR DELIVERY OF NATAMYCIN SOLID LIPID NANOPARTICLE LOADED MUCOADHESIVE GEL: FORMULATION, CHARACTERIZATION AND IN VIVO STUDY

Objective: This study aimed to develop a novel topical ocular system of natamycin (NAT) by formulating and evaluating of NAT-solid lipid nanoparticle (SLN) loaded on mucoadhesive gels to improve its therapeutic activity and reduce the frequency of dosage to assist patient compliance.&#x0D; Methods: SLNs were prepared using lipids and Tween 80 or Pluronic F127 as stabilizers via modified high shear homogenization and ultrasound techniques. The prepared SLNs were characterized for particle size (PS), zeta potential (ZP), polydispersity index (PI), and entrapment efficiency percentage (EE %). The morphological examination for chosen SLNs was done using a transmission electron microscope (TEM). Carbapol 940 and Hydroxypropyl methylcellulose (HPMC) was incorporated with selected NAT-SLNs to form mucoadhesive gels. The prepared NAT-SLN gels were evaluated for drug content, mucoadhesion force, release study, and in vitro microbiological activity. In vivo study for the chosen formulae was done to evaluate its efficacy against keratitis in rabbits.&#x0D; Results: NAT-SLNs exhibited high EE % up to 99.167% and PS ranging from 128.35 to 1719.5 nm, with negatively charged ZP that confirmed the stability of SLNs. The NAT-SLN gels provided the high mucoadhesive force with a controlled release manner compared with the marketed-product MP. The in vivo experimental studies and histopathological examination showed the superiority of G2 (NAT-SLN (5% Pluronic F127 and 1:1 mixed lipid) 4% HPMC) over MP against Candida keratitis.&#x0D; Conclusion: According to the obtained results, G2 provided an effective pharmaceutical system against fungal keratitis in a controlled release manner compared with MP for reducing dosage frequency.