Nanosuspension Based In Situ Gelling Nasal Spray of Carvedilol: Development, In Vitro and In Vivo Characterization

The objective of the present investigation was to develop in situ gelling nasal spray formulation of carvedilol (CRV) nanosuspension to improve the bioavailability and therapeutic efficiency. Solvent precipitation–ultrasonication method was opted for the preparation of CRV nanosuspension which further incorporated into the in situ gelling polymer phase. Optimized formulation was extensively characterized for various physical parameters like in situ gelation, rheological properties and in vitro drug release. Formation of in situ gel upon contact with nasal fluid was conferred via the use of ion-activated gellan gum as carrier. In vivo studies in rabbits were performed comparing the nasal bioavailability of CRV after oral, nasal, and intravenous administration. Optimized CRV nanosuspension prepared by combination of poloxamer 407 and oleic acid showed good particle size [d (0.9); 0.19 μm], zeta potential (+10.2 mV) and polydispersity (span; 0.63). The formulation containing 0.5% w/v gellan gum demonstrated good gelation ability and desired sustained drug release over period of 12 h. In vivo pharmacokinetic study revealed that the absolute bioavailability of in situ nasal spray formulation (69.38%) was significantly increased as compared to orally administered CRV (25.96%) with mean residence time 8.65 h. Hence, such in situ gel system containing drug nanosuspension is a promising approach for the intranasal delivery in order to increase nasal mucosal permeability and in vivo residence time which altogether improves drug bioavailability.KEY WORDS: bioavailability, Carvedilol, in situ gel, intranasal, nanosuspension     

Thermoreversible Nasal In situ Gel of Venlafaxine Hydrochloride: Formulation, Characterization, and Pharmacodynamic Evaluation

In order to improve the bioavailability of the antidepressant drug, venlafaxine hydrochloride, in situ mucoadhesive thermoreversible gel, was formulated using Lutrol F127 (18%) as a thermo gelling polymer. Mucoadhesion was modulated by trying carbopol 934, PVP K30, HPMC K4M, sodium alginate, tamarind seed gum, and carrageenan as mucoadhesive polymers. Results revealed that as the concentration of mucoadhesive polymer increased the mucoadhesive strength increased but gelation temperature decreased. Formulation was optimized on the basis of clarity, pH, gelation temperature, mucoadhesive strength, gel strength, viscosity, drug content, diffusion through sheep nasal mucosa, histopathological evaluation of mucosa, and pharmacodynamic study in rats. Final formulation T5 containing 18% Lutrol F127 and 0.3% PVP K30 was considered as an optimized formulation. T5 released 97.86 ± 0.073% drug in 150 min with a flux of 0.1545 mg cm⁻² min⁻¹ and gelation temperature 31.17 ± 0.30°C. Histopathological evaluation of nasal mucosa revealed that T5 formulation was safe for nasal administration as it caused no damage to nasal epithelium. From the results of pharmacodynamic study, mainly forced swim test (FST), it was concluded that venlafaxine hydrochloride was more effective as an antidepressant by nasal route as in situ gel nasal drops in comparison to oral administration of equivalent dose.Key words: lutrol F127, mucoadhesive, nasal in situ gel, thermoreversible, venlafaxine HCl     

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

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

Development and Characterization of Mucoadhesive <Emphasis Type="Italic">In Situ</Emphasis> Nasal Gel of Midazolam Prepared with <Emphasis Type="Italic">Ficus carica</Emphasis> Mucilage

The objective of the present study was to prepare mucoadhesive in situ nasal gels with mucilage isolated from fig fruits (Ficus carica, family: Moraceae) containing midazolam hydrochloride. Nasal gels of midazolam were prepared using three different concentrations (0.5%, 1.0% and 1.5% w/v) of F. carica mucilage (FCM) and synthetic polymers (hydroxypropylmethyl cellulose and Carbopol 934). Evaluation of FCM showed that it was as safe as the synthetic polymers for nasal administration. In situ gels were prepared with mixture Pluronic F127 and mucoadhesive agents. Evaluation of the prepared gels was carried out, including determination of viscosity, texture profile analysis and mucoadhesive strength. In vitro drug permeation study was conducted with the gels prepared with and without permeation enhancer (0.5% w/v sodium taurocholate) using excised goat nasal mucosa. In vitro permeation profiles were evaluated, and histological study of nasal mucosae before and after permeation study was also conducted to determine histological change, if any. In vivo experiments conducted in rabbits further confirmed that in situ nasal gels provided better bioavailability of midazolam than the gels prepared from synthetic mucoadhesive polymers. It was observed that the nasal gel containing 0.5% FCM and 0.5% sodium taurocholate exhibited appropriate rheological, mechanical and mucoadhesive properties and showed better drug release profiles. Moreover, this formulation produced no damage to the nasal mucosa that was used for the permeation study, and absolute bioavailability was also higher compared to gels prepared from synthetic polymers.     

Formulation and Evaluation of <Emphasis Type="Italic">In Situ</Emphasis> Gelling Systems for Intranasal Administration of Gastrodin

Gastrodin is the major bioactive constituent of the traditional Chinese drug “Tianma.” It is used in the treatment of some nervous system diseases and can be transported to the brain via intranasal administration. In the current paper, the development of a novel ion-activated in situ gelling system for the nasal delivery of gastrodin is discussed. An in situ perfusion model was used to determine the absorption-rate constant of gastrodin through rat nasal mucosa. The optimal formulation was determined by measuring the critical cation concentration, anti-dilution capacity, gel expansion coefficient, water-holding capacity, and adhesive capacity. The best formulation consisted of 10% gastrodin, 0.5% deacetylated gellan gum as the gelatinizer, and 0.03% ethylparaben as the preservative. The rheological properties of gastrodin nasal in situ gels were also investigated. The viscosity and elasticity sharply increased at temperatures below 25°C. When physiological concentrations of cations were added into the preparation, the mixture gelled into a semi-solid. The results of an accelerated stability test show that gastrodin nasal in situ gels can be stable for more than 2 years. Mucociliary toxicity was evaluated using the in situ toad palate model and the rat nasal mucociliary method; both models demonstrated no measurable ciliotoxicity. Pharmacodynamic studies suggest that similar acesodyne and sedative effects were induced following intranasal administration of 50 mg/kg gastrodin nasal in situ gels or oral administration of 100 mg/kg gastrodin solution. The in situ gel preparation is a safe and effective nasal delivery system for gastrodin.     

Thermally Triggered Mucoadhesive In Situ Gel of Loratadine: β-Cyclodextrin Complex for Nasal Delivery

The aim of the present study was to increase the solubility of an anti-allergic drug loratadine by making its inclusion complex with β-cyclodextrin and to develop it’s thermally triggered mucoadhesive in situ nasal gel so as to overcome first-pass effect and consequently enhance its bioavailability. A total of eight formulations were prepared by cold method and optimized by 2³ full factorial design. Independent variables (concentration of poloxamer 407, concentration of carbopol 934 P, and pure drug or its inclusion complex) were optimized in order to achieve desired gelling temperature with sufficient mucoadhesive strength and maximum permeation across experimental nasal membrane. The design was validated by extra design checkpoint formulation (F9) and Pareto charts were used to help eliminate terms that did not have a statistically significant effect. The response surface plots and possible interactions between independent variables were analyzed using Design Expert Software 8.0.2 (Stat Ease, Inc., USA). Faster drug permeation with zero-order kinetics and target flux was achieved with formulation containing drug: β-cyclodextrin complex rather than those made with free drug. The optimized formulation (F8) with a gelling temperature of 28.6 ± 0.47°C and highest mucoadhesive strength of 7,676.0 ± 0.97 dyn/cm² displayed 97.74 ± 0.87% cumulative drug permeation at 6 h. It was stable for over 3 months and histological examination revealed no remarkable damage to the nasal tissue.     

Platelet Lysate Mucohadesive Formulation to Treat Oral Mucositis in Graft <Emphasis Type="Italic">Versus</Emphasis> Host Disease Patients: A New Therapeutic Approach

Optimal treatment of oral mucositis (OM) due to graft versus host disease (GvHD) is currently not available. Platelet-derived growth factors (PDGFs) have high capability for tissue healing and may play a role in repairing the mucosal barrier. The aim of the present work was to develop a mucoadhesive formulation to administer platelet lysate to oral cavity prolonging contact time of platelet lysate with oral mucosa. The mucoadhesive formulation was characterized for in vitro properties (PDGF-AB concentration, mucoadhesive properties, cytotoxicity, fibroblast proliferation, wound healing). Moreover, a preliminary clinical study on seven GvHD patients with OM refractory to other therapies was conducted, to evaluate feasibility, safety, and efficacy. GVPL (mucoadhesive gel vehicle mixed with platelet lysate)showed good mucoadhesive properties; additionally, it was characterized by good biocompatibility in vitro on fibroblasts and it was able to enhance fibroblast proliferation and wound healing, maintaining the efficacy for up to 14 days following storage at 2–8°C. In vivo, clinical response was good-to-complete in five, fair in one, none in the remaining one. The in vitro results indicate that GVPL has optimal mucoadhesive and healing enhancer properties, maintained over time (up to 14 days); preliminary clinical results suggest that oral application of platelet lysate-loaded mucoadhesive formulation is feasible, safe, well tolerated, and effective. A larger controlled randomized study is needed.     

Formulation and Evaluation of Fast Dissolving Films for Delivery of Triclosan to the Oral Cavity

The present investigation was undertaken with the objective of formulating TC containing fast dissolving films for local delivery to oral cavity. Various film forming agents, film modifiers and polyhydric alcohols were evaluated for optimizing the composition of fast dissolving films. The potential of poloxamer 407 and hydroxypropyl-β- cyclodextrin (HPBCD) to improve solubility of TC was investigated. Fast dissolving films containing hydroxypropyl methylcellulose (HPMC), xanthan gum, and xylitol were formulated. Use of poloxamer 407 and HPBCD resulted in significant improvement in the solubility of TC. Fast dissolving films containing TC-HPBCD complex and TC-Poloxamer 407 were formulated and were evaluated for the in vitro dissolution profile and in vitro microbiological assay. Films containing TC-Poloxamer 407 exhibited better in vitro dissolution profile and in vitro antimicrobial activity as compared to the films containing TC-HPBCD complex. Effect of incorporation of eugenol on the in vivo performance of TC-Poloxamer 407 containing films was evaluated in human volunteers. Eugenol containing films improved the acceptability of TC-Poloxamer 407 films with respect to taste masking and mouth freshening without compromising the in vivo dissolution time.     

A Novel Transdermal Delivery System for the Anti-Inflammatory Lumiracoxib: Influence of Oleic Acid on <Emphasis Type="Italic">In Vitro</Emphasis> Percutaneous Absorption and <Emphasis Type="Italic">In Vivo</Emphasis> Potential Cutaneous Irritation

Transdermal delivery of non-steroidal anti-inflammatory drugs may be an interesting strategy for delivering these drugs to the diseased site, but it would be ineffective due to low skin permeability. We investigated whether oleic acid (OA), a lipid penetration enhancer in poloxamer gels named poloxamer-based delivery systems (PBDS), can improve lumiracoxib (LM) delivery to/through the skin. The LM partition coefficient (K) studies were carried out in order to evaluate the drug lipophilicity grade (K _{octanol/buffer}), showing values >1 which demonstrated its high lipophilicity. Both in vitro percutaneous absorption and skin retention studies of LM were measured in the presence or absence of OA (in different concentrations) in PBDS using porcine ear skin. The flux of in vitro percutaneous absorption and in vitro retention of LM in viable epidermis increased in the presence of 10.0% (w/w) OA in 25.0% (w/w) poloxamer gel. In vivo cutaneous irritation potential was carried out in rabbits showing that this formulation did not provide primary or cumulative cutaneous irritability in animal model. The results showed that 25.0% poloxamer gel containing 10.0% OA is potential transdermal delivery system for LM.     

Formulation and In Vitro Evaluation of Salbutamol Sulphate In Situ Gelling Nasal Inserts

The aim of this study was to formulate salbutamol sulfate (SS), a model drug, as mucoadhesive in situ gelling inserts having a high potential as nasal drug delivery system bypassing the first-pass metabolism. In situ gelling inserts, each containing 1.4% SS and 2% gel-forming polymer, hydroxypropyl methylcellulose (HPMC), carboxymethylcellulose sodium (CMC Na), sodium alginate (AL), and chitosan (CH) were prepared. The inserts were investigated for their different physicochemical properties. The weight of inserts was 16–27 mg, drug content was 3.9–4.2 mg, thickness ranged between 15 and 28 μm and surface pH was 5–7. Cumulative drug released from the inserts exhibited extended release for more than 10 h following the decreasing order: CH > AL > CMC Na > HPMC. The drug release from CMC Na and AL inserts followed zero-order kinetics while HPMC and CH inserts exhibited non-Fickian diffusion mechanism. The inserts exhibited different water uptake (7–23%) with the smallest values for CH. Differential scanning calorimetry study pointed out possible interaction of SS and oppositely charged anionic polymers (CMC Na and AL). The mucoadhesive in situ gelling inserts exhibited satisfactory mucoadhesive and extended drug release characteristics. The inserts could be used for nasal delivery of SS over about 12 h; bypassing the hepatic first-pass metabolism without potential irritation.KEY WORDS: in situ gelling inserts, mucoadhesion, nasal delivery, salbutamol sulfate     

Dual-Drug Delivery System Based on <Emphasis Type="Italic">In Situ</Emphasis> Gel-Forming Nanosuspension of Forskolin to Enhance Antiglaucoma Efficacy

The present study was designed to improve the bioavailability of forskolin by the influence of precorneal residence time and dissolution characteristics. Nanosizing is an advanced approach to overcome the issue of poor aqueous solubility of active pharmaceutical ingredients. Forskolin nanocrystals have been successfully manufactured and stabilized by poloxamer 407. These nanocrystals have been characterized in terms of particle size by scanning electron microscopy and dynamic light scattering. By formulating Noveon AA-1 polycarbophil/poloxamer 407 platforms, at specific concentrations, it was possible to obtain a pH and thermoreversible gel with a pH_gel/T _gel close to eye pH/temperature. The addition of forskolin nanocrystals did not alter the gelation properties of Noveon AA-1 polycarbophil/poloxamer 407 and nanocrystal properties of forskolin. The formulation was stable over a period of 6 months at room temperature. In vitro release experiments indicated that the optimized platform was able to prolong and control forskolin release for more than 5 h. The in vivo studies on dexamethasone-induced glaucomatous rabbits indicated that the intraocular pressure lowering efficacy for nanosuspension/hydrogel systems was 31% and lasted for 12 h, which is significantly better than the effect of traditional eye suspension (18%, 4–6 h). Hence, our investigations successfully prove that the pH and thermoreversible polymeric in situ gel-forming nanosuspension with ability of controlled drug release exhibits a greater potential for glaucoma therapy.     

Design and Formulation of Mebeverine HCl Semisolid Formulations for Intraorally Administration

Gel formulations of mebeverine hydrochloride (MbHCl) containing hydroxypropylmethylcellulose (HPMC), metolose (MTL), and poloxamer 407 (PLX) were prepared to be used in the treatment of different oral painful conditions. HPMC was used as a mucoadhesive gel base while MTL and PLX were used to prepare sol–gel thermosensitive gels. MTL and PLX formulations showed proper sol–gel transition temperature for intraoral application. Formulations were evaluated in terms of their viscosity, mechanical properties, mucoadhesivity, stability, and in vitro drug release. The formulation prepared with 2% of HPMC K100M provided the highest viscosity at room temperature. However, the viscosity of HPMC–PLX mixture showed a significant increase at body temperature. The greatest mucoadhesion was also noted in HPMC–PLX combinations. Texture profile analysis exhibited the differences of the adhesion, hardness, elasticity, cohesiveness, and compressibility of the formulations. The release profiles of MbHCl were obtained, and non-Fickian release was observed from all the formulations. The formulations were stored at different temperature and relative humidity. No significant changes were observed at the end of the 3 months. HPMC–PLX formulation of MbHCl was chosen for in vivo studies, and it remained longer than dye solution on the rabbit’s intraoral mucosal tissue. It was found worthy of further clinical evaluation.     

Development of Satranidazole Mucoadhesive Gel for the Treatment of Periodontitis

The aim of the paper was to develop satranidazole-containing mucoadhesive gel for the treatment of periodontitis. Different mucoadhesive gels were prepared, using various gelling agents like sodium carboxymethylcellulose (SCMC), poloxamer 407, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and the mucoadhesive polymer carbopol 934P. The selected formulations (based on the mucoadhesive force) were studied for different mechanical properties, such as mucoadhesive strength, hardness, compressibility, adhesiveness, and cohesiveness through Texture Profile Analyzer. In vitro satranidazole release from the prepared formulations was also determined and compared with marketed preparation of metronidazole (Metrogyl® gel). The formulation SC30 (containing SCMC 3% w/v) showed maximum mucoadhesive strength (167.72 ± 3.76 g) and adhesiveness (−46.23 ± 0.34 N mm), with low hardness (9.81 ± 0.04 N) and compressibility (40.05 ± 0.48 N mm) and moderate cohesiveness (0.87 ± 0.01). SC30 formulation exhibited long-term release. Thus, SC30 gel was evaluated for its clinical effectiveness along with marketed metronidazole gel. At the end of the study (42 days of clinical studies), both formulations were found to significantly reduce the probing depth, plaque index, gingival index, calculus criteria, and bleeding index. However, the SC30 gel was more effective in reducing the above parameters than marketed metronidazole gel. This study confirmed the acceptability and effectiveness of satranidazole gel for treatment of periodontitis.Key words: mucoadhesive gel, periodontitis, satranidazole, texture profile analysis     

The Impact of Vehicles on the Mucoadhesive Properties of Orally Administrated Nanoparticles: a Case Study with Chitosan-4-Thiobutylamidine Conjugate

The aim of this study was to evaluate the impact of various vehicles on mucoadhesive properties of thiolated chitosan nanoparticles both in vitro and in vivo. Nanoparticles (NPs) were prepared by in situ gelation technique followed by labeling with fluorescein diacetate. Comparative studies on mucoadhesion were done with these thiolated chitosan NPs and unmodified chitosan NPs (control). The obtained nanoparticles displayed a mean diameter of 164.2 ± 6.9 nm and a zeta potential of 21.5 ± 5 mV. In an in vitro adhesion study, unhydrated thiolated NPs adhered strongly to freshly excised porcine small intestine, which was more than threefold increase compared to the control. In contrast, in the presence of various vehicles (PEG 300, miglyol 840, PEG 6000, cremophor EL, and caprylic triglyceride), the mucoadhesive properties of thiolated NPs were comparatively weak. Thiolated NPs suspended in caprylic triglyceride, for example, had a percent mucoadhesion of 22.50 ± 5.35% on the mucosa. Furthermore, results from in vivo mucoadhesion studies revealed that the dry form of nanoparticles exhibits the strongest mucoadhesion, followed by nanoparticles suspended in PEG 300, miglyol, and 100 mM phosphate buffer, in that order. Three hours after administration, the gastrointestinal residence time of the dry form of thiolated NPs was up to 3.6-fold prolonged. These findings should contribute to the design of highly effective oral mucoadhesive nanoparticulate drug delivery systems.     

Platelet Lysate Mucohadesive Formulation to Treat Oral Mucositis in Graft Versus Host Disease Patients: A New Therapeutic Approach

Optimal treatment of oral mucositis (OM) due to graft versus host disease (GvHD) is currently not available. Platelet-derived growth factors (PDGFs) have high capability for tissue healing and may play a role in repairing the mucosal barrier. The aim of the present work was to develop a mucoadhesive formulation to administer platelet lysate to oral cavity prolonging contact time of platelet lysate with oral mucosa. The mucoadhesive formulation was characterized for in vitro properties (PDGF-AB concentration, mucoadhesive properties, cytotoxicity, fibroblast proliferation, wound healing). Moreover, a preliminary clinical study on seven GvHD patients with OM refractory to other therapies was conducted, to evaluate feasibility, safety, and efficacy. GVPL (mucoadhesive gel vehicle mixed with platelet lysate)showed good mucoadhesive properties; additionally, it was characterized by good biocompatibility in vitro on fibroblasts and it was able to enhance fibroblast proliferation and wound healing, maintaining the efficacy for up to 14 days following storage at 2–8°C. In vivo, clinical response was good-to-complete in five, fair in one, none in the remaining one. The in vitro results indicate that GVPL has optimal mucoadhesive and healing enhancer properties, maintained over time (up to 14 days); preliminary clinical results suggest that oral application of platelet lysate-loaded mucoadhesive formulation is feasible, safe, well tolerated, and effective. A larger controlled randomized study is needed.KEY WORDS: in vitro proliferation and wound healing test, in vivo assessment in graft versus host disease, mucositis, platelet lysate growth factors     

Design and In Vitro/In Vivo Evaluation of Novel Mucoadhesive Buccal Discs of an Antifungal Drug: Relationship Between Swelling, Erosion, and Drug Release

Two groups of fluconazole mucoadhesive buccal discs were prepared: (a) Fluconazole buccal discs prepared by direct compression containing bioadhesive polymers, namely, Carbopol 974p (Cp), sodium carboxymethyl cellulose (SCMC), or sodium alginate (SALG) in combination with hydroxypropyl methylcellulose (HPMC) or hydroxyethyl cellulose (HEC). (b) Fluconazole buccal discs prepared by freeze drying containing different polymer combinations (SCMC/HPMC, Cp/HPMC, SALG/HPMC, and chitosan/SALG). The prepared discs were evaluated by investigating their release pattern, swelling capacity, mucoadhesion properties, and in vitro adhesion time. In vivo evaluation of the buccal disc and in vivo residence times were also performed. Fluconazole salivary concentration after application of fluconazole buccal systems to four healthy volunteers was determined using microbiological assay and high-performance liquid chromatography. SCMC/HPMC buccal disc prepared by direct compression could be considered comparatively superior mucoadhesive disc regarding its in vitro adhesion time, in vivo residence time, and in vitro/in vivo release rates of the drug. Determination of the amount of drug released in saliva after application of the selected fluconazole disc confirmed the ability of the disc to deliver the drug over a period of approximately 5 h and to reduce side effects and possibility of drug interaction encountered during systemic therapy of fluconazole, which would be beneficial in the case of oral candidiasis.     

Influence of gelling agents on culture medium gel strength, water availability, tissue water potential, and maturation response in embryogenic cultures of Pinus strobus L.

Summary Maturation of somatic embryos of Pinus strobus L. was evaluated on media containing various types (agars and gellan gum), brands and concentrations of gelling agents in the presence of 80 μM ABA and 0.09 M sucrose. The media were characterized with respect to gel strength, water potential and water availability. Embryogenic tissue and somatic embryos cultured on medium with various concentrations of gellan gum were used to determine their water potential (Ψ). Regardless of the type of gelling agent used, gel strength increased with gelling agent concentration and was critical to the maturation response. High gel strength was associated with reduced water availability from the medium to the cultures. The water potential of gelled maturation medium remained constant between 0.4 and 1.0% gellan gum. It is concluded that the embryogenic tissue was exposed to varying amounts of water at the onset of and during the culture period, and that the amount of water in the culture environment in turn influenced the maturation response. Cotyledonary somatic embryos derived from gellan gum medium of high gel strength had a lower Ψ than somatic embryos matured on medium of lower gel strength. Once somatic embryos developed to the cotyledonary stage on the maturation medium, they were transferred to the germination medium. The germination frequency and the number of morphologically normal germinants were higher for somatic embryos matured on medium of high gel strength. Raising the concentration of the gelling agent in the maturation medium may be an alternative to the use of solutes to restrict water available to the embryogenic cultures.     

In Vitro and In Vivo Characteristics of a Thermogelling Rectal Delivery System of Etodolac

Rectal etodolac–Poloxamer gel systems composed of Poloxamer and bioadhesive polymers were developed and evaluated. Hydroxypropylmethyl cellulose, poly)vinyl) pyrrolidone, methyl cellulose, hydroxyethylcellulose, and carbopol were examined as mucoadhesive polymers. The characteristics of the rectal gels differed according to the properties of mucoadhesive polymers. The physicochemical properties such as gelation temperature, gel strength, and bioadhesive force of various formulations were investigated. The analysis of release mechanism showed that the release of etodolac was proportional to the square root of time, indicating that etodolac might be released from the suppositories by Fickian diffusion. The anti-inflammatory effect of etodolac–Poloxamer gel system was also studied in rats. Moreover, liquid suppository of etodolac did not cause any morphological damage to the rectal tissues. These results suggested that in situ gelling liquid suppository with etodolac and mucoadhesive polymer was a physically safe, convenient, and effective rectal dosage form for etodolac.     

Topical Niosome Gel Containing an Anthocyanin Complex: a Potential Oral Wound Healing in Rats

Anthocyanins from dietary sources showing potential benefits as anti-inflammatory in oral lesions were developed as an anthocyanin complex (AC), comprised of extracts of Zea mays (CC) and Clitoria ternatea (CT), and formulated into a niosome gel to prove its topical oral wound healing in vitro and in vivo investigations. The AC formed nano-sized clusters of crystalline-like aggregates, occurring through both intra- and inter-molecular interactions, resulting in delivery depots of anthocyanins, following encapsulation in niosomes and incorporation into a mucoadhesive gel. In vitro permeation of anthocyanins was improved by complexation and further enhanced by encapsulation in niosomes. Collagen production in human gingival fibroblasts was promoted by AC and AC niosomes, but not CC or CT. The in vivo wound healing properties of AC gel (1 and 10%), AC niosome gel (1 and 10%), fluocinolone acetonide gel, and placebo gel were investigated for incisional wounds in the buccal cavities of Wistar rats. AC gel and AC niosome gel both reduced wound sizes after 3 days. AC niosome gel (10%) gave the highest reduction in wound sizes after day 3 (compared to fluocinolone acetonide gel, p?<?0.05), and resulted in 100% wound healing by day 5. Histological observations of cross-sectioned wound tissues revealed the adverse effects of fluocinolone gel and wound healing potential of AC niosome gel. Topical application of AC niosome gel exhibited an anti-inflammatory effect and promoted oral wound closure in rats, possibly due to the improved mucosal permeability and presence of delivery depots of AC in the niosome gel.     

Design and Development of Gliclazide Mucoadhesive Microcapsules: In Vitro and In Vivo Evaluation

In this study an attempt was made to prepare mucoadhesive microcapsules of gliclazide using various mucoadhesive polymers designed for oral controlled release. Gliclazide microcapsules were prepared using sodium alginate and mucoadhesive polymer such as sodium carboxymethyl cellulose (sodium CMC), carbopol 934P or hydroxy propylmethyl cellulose (HPMC) by orifice-ionic gelation method. The microcapsules were evaluated for surface morphology and particle shape by scanning electron microscope. Microcapsules were also evaluated for their microencapsulation efficiency, in vitro wash-off mucoadhesion test, in vitro drug release and in vivo study. The microcapsules were discrete, spherical and free flowing. The microencapsulation efficiency was in the range of 65–80% and microcapsules exhibited good mucoadhesive property in the in vitro wash off test. The percentage of microcapsules adhering to tissue at pH 7.4 after 6 h varied from 12–32%, whereas the percentage of microcapsules adhering to tissue at pH 1.2 after 6 h varied from 35–68%. The drug release was also found to be slow and extended for more than 16 h. In vivo testing of the mucoadhesive microcapsules in diabetic albino rats demonstrated significant antidiabetic effect of gliclazide. The hypoglycemic effect obtained by mucoadhesive microcapsules was for more than 16 h whereas gliclazide produced an antidiabetic effect for only 10 h suggesting that mucoadhesive microcapsules are a valuable system for the long term delivery of gliclazide.