Loratadine bioavailability via buccal transferosomal gel: formulation,statistical optimization,in vitro/in vivo characterization,and pharmacokinetics in human volunteers

Loratadine (LTD) is an antihistaminic drug that suffers limited solubility, poor oral bioavailability (owing to extensive first-pass metabolism), and highly variable oral absorption. This study was undertaken to develop and statistically optimize transfersomal gel for transbuccal delivery of LTD. Transfersomes bearing LTD were prepared by conventional thin film hydration method and optimized using sequential Quality-by-Design approach that involved Placket–Burman design for screening followed by constrained simplex-centroid design for optimization of a Tween-80/Span-60/Span-80 mixture. The transferosomes were characterized for entrapment efficiency, particle size, and shape. Optimized transferosomes were incorporated in a mucoadhesive gel. The gel was characterized for rheology, ex vivo permeation across chicken pouch buccal mucosa, in vitro release, and mucoadhesion. Pharmacokinetic behavior of LTD formulations was investigated in healthy volunteers following administration of a single 10-mg dose. Optimal transferosomes characterized by submicron size (380?nm), spherical shape and adequate loading capacity (60%) were obtained by using quasi-equal ratio surfactant mixture. In terms of amount permeated, percentage released, and mucoadhesion time, the transferosomal gel proved superior to control, transferosome-free gel. Bioavailability of the transferosomal gel was comparable to Claritin® oral tablets. However, inter-individual variability in C_max and AUC was reduced by 76 and 90%, respectively, when the buccal gel was used. Linear Correlation of in vitro release with in vivo buccal absorption fractions was established with excellent correlation coefficient (R²>0.97). In summary, a novel buccal delivery system for LTD was developed. However, further clinical investigation is warranted to evaluate its therapeutic effectiveness and utility.     

Absorption-improving effects of chitosan oligomers based on their mucoadhesive properties: a comparative study on the oral and pulmonary delivery of calcitonin

Effects of chitosan oligomers with different types and varying concentrations on the intestinal and pulmonary absorptions of calcitonin were investigated in rats by an in situ closed loop method and an in vivo pulmonary absorption experiment, respectively. Various chitosan oligomers demonstrated different efficiencies in improving the intestinal and pulmonary absorptions of calcitonin, and chitosan hexamer with the optimal concentration of 0.5% (w/v) showed the greatest absorption enhancing effect. Moreover, pharmacodynamic parameters of calcitonin after its coadministration intrapulmonarily with various chitosan oligomers were consistently larger than that in the intestinal delivery, indicating the superior potential of pulmonary administration for systemic delivery of calcitonin. Furthermore, various chitosan oligomers neither obviously increased release amounts of protein nor activities of lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF), revealing the safety of these chitosan oligomers to lung tissue. In addition, bioadhesions of various chitosan oligomers were well consistent with their absorption enhancing effects in the absorption experiment, suggesting the contribution of mucoadhesive properties of chitosan oligomers to their absorption improving effects. Taken together, chitosan oligomers, especially chitosan hexamer, can effectively improve the intestinal and pulmonary absorptions of calcitonin partly due to the mucoadhesion between positive chitosan oligomers and negative mucus in the membrane.     

Physicochemical and in vitro mucoadhesive properties of microparticles/discs of betamethasone for the management of oral lichen planus

This study involved the preparation and evaluation of buccal-mucoadhesive microparticles/discs of bethamethasone disodium phosphate (BDSP). The microparticles were prepared using the emulsion solvent diffusion method. Microparticles were prepared and characterized by encapsulation efficiency particle size, Fourier Transform Infra Red (FTIR) spectrums, Differential Scanning Calorimetric (DSC) thermograms and mucoadhesive properties. FTIR studies reported that BDSP was changed to bethamethasone base molecule inside the intact microparticles. The best drug to polymers ratio in microparticles was F₁ containing 50?mg drug, 50?mg HPMC (as non-ionic and hydrophilic polymer) and 50?mg carbomer 934p (an anionic mucoadhesive polymer). The production yield of F1 microparticles was calculated as 78.60% with loading efficiency of about 65.14% and the mean particle size was also measured as 281.84?μm. It was proposed that during the microparticle preparation procedure, water soluble salt of the drug may be converted to the base which could be more effective in the buccal mucosa due to its higher partition coefficient and lipophilicity. The highest and lowest releases resulted from the discs prepared from F₁ and F₄, respectively, compared with the commercial tablet and untreated drug powder (p?<?0.05). The data revealed that the discs exhibited good percentage of mucoadhesion (F₁, 326?g/cm²). It may be concluded that drug loaded buccal-mucoadhesive microparticles are a suitable delivery system for BDSP, and may be used in the effective management of lichen planus.     

Chitosan–gum arabic polyelectrolyte complex films: physicochemical,mechanical and mucoadhesive properties

By blending chitosan (CS) and gum arabic (GA), a powerful biomaterial complex might be obtained due to the unique properties of CS and the low viscosity and good emulsifying properties of GA. The objectives of this study were to prepare and examine the properties of dispersions and films of CS and GA as a function of the mixing weight ratio, pH value and molecular weight of CS. The dispersions were characterized by turbidity, zeta potential and cytotoxicity and then the dispersions were cast into films. Physicochemical properties of the film were performed. CS–GA dispersions exhibited higher turbidity and a lower zeta potential with an increase in the GA ratio. Continuous films of the CS–GA could be formed at all ratios. CS and GA could molecularly interact via electrostatic forces and intermolecular hydrogen bonding. The CS–GA (1:0.5) films exhibited relatively low water uptake, erosion, water vapor permeability and puncture strength compared to the CS films. Furthermore, the CS–GA films demonstrated good mucoadhesive properties, allowing for adhesion to the mucosal membrane. Based on these results, it could be advantageous to use CS–GA films as film formers for the formulation of coatings and drug delivery systems.     

口腔粘膜粘附给药系统

本文对口腔粘膜粘附给药系统这一新型给药系统从口腔粘膜的结构与分类、粘膜粘附的理论及影响因素、处方的设计、剂型、质量评价等方面作了介绍。     

The efficacy of the bioadhesive patches containing licorice extract in the management of recurrent aphthous stomatitis

This study evaluated the efficacy of licorice bioadhesive hydrogel patches to control the pain and reduce the healing time of recurrent aphthous ulcer.This study was carried out in three episodes of ulcers: in the first episode of ulcer, all 15 patients were asked to record their baseline individual pain level by a visual analog scale. In the second and third episodes, comparative and consecutive subjective and objective evaluations of the bioadhesive were done. The effects of the following variables were investigated: (1) VAS pain score for 5 consecutive days, (2) profile of aphthous ulcers on days 3 and 5, (3) time to complete relief of pain and healing of the ulcers, (4) diameter of the lesions and necrotic zone.A significant reduction in VAS was recorded following application of the licorice patches on days 2, 3, 4 and 5 compared with the no-treatment group (p < 0.001). Licorice patches caused a significant reduction in the diameter of the inflammatory halo and necrotic center compared with the placebo group (p = 0.03).According to the results of this study, licorice bioadhesive can be effective in the reduction of pain and of the inflammatory halo and necrotic center of aphthous ulcers.     

正交试验法优选山黄口腔贴片的处方

目的制备用于治疗口腔溃疡的山黄口腔贴片。方法以口腔贴片的黏附力、药物释放速率等为指标,通过正交实验,筛选口腔贴片的处方。结果筛选得到优化处方为：淀粉与微晶纤维素的质量比为3：2,羟丙甲纤维素（K15M CR）用量为15％。山黄方中部分药材提取后得干浸膏粉,加入方中其他药材细粉及上述辅料,以体积分数70％乙醇为润湿剂,湿法制粒并压片,片的一面涂防粘层。其体外黏附力及释药速率均较理想。结论所筛选的山黄口腔贴片处方稳定可行。     

Freeze-Dried Matrices Based on Polyanion Polymers for Chlorhexidine Local Release in the Buccal and Vaginal Cavities

Chlorhexidine (CLX) is a wide spectrum cationic antimicrobial used for prevention and treatment of infections of buccal and vaginal cavities. To increase the residence time of CLX-based formulations at the application site and consequently reduce the daily dose frequency, new formulations composed of mucoadhesive polymers should be designed. The objective of this work was the development of matrices based on polyanionic polymers, such as sodium alginate, carboxymethylcellulose, xanthan gum and sodium hyaluronate, aimed to prolong the local release of CLX into the buccal or vaginal cavity. Matrices were prepared by freeze-drying and comply with 2 different preparative methods and characterized in terms of resistance to compression, water uptake ability, mucoadhesion, in vitro drug release behavior and antimicrobial activity toward representative pathogens of buccal and vaginal cavities. Results showed that the selection of suitable polymers associated to the adequate preparative method allowed to modulate matrix ability to hydrate, adhere to the mucosa and release the drug as well as to exert antimicrobial activity. In particular, matrix based on sodium hyaluronate was found to be the best performing formulation and could represent a versatile system for local release of CLX with potential application in both buccal and vaginal cavities.     

Mucoadhesive buccal tablets containing silymarin Eudragit-loaded nanoparticles: formulation,characterisation and ex vivo permeation

Eudragit-loaded silymarin nanoparticles (SNPs) and their formulation into buccal mucoadhesive tablets were investigated to improve the low bioavailability of silymarin through buccal delivery. Characterisation of SNPs and silymarin buccal tablets (SBTs) containing the optimised NPs were performed. Ex vivo permeability of nominated SBTs were assessed using chicken pouch mucosa compared to SNPs and drug suspension followed by histopathological examination. Selected SNPs had a small size (<150?nm), encapsulation effciency (>77%) with drug release of about 90% after 6?h. For STBs, all physicochemical parameters were satisfactory for different polymers used. DSC and FT-IR studies suggested the presence of silymarin in an amorphous state. Ex vivo permeation significantly emphasised the great enhancement of silymarin permeation after NPs formation and much more increase after formulating into BTs relative to the corresponding drug dispersion with confirmed membrane integrity. Incorporation of SNPs into BTs could be an efficient vehicle for delivery of silymarin.     

Bioadhesive Chitosan-Coated Cationic Nanoliposomes With Improved Insulin Encapsulation and Prolonged Oral Hypoglycemic Effect in Diabetic Mice

Oral administration of insulin is hampered by the lack of carriers that can efficiently achieve high encapsulation, avoid gastric degradation, overcome mucosal barriers, and prolong the hypoglycemic effect. Chitosan (CS)-coated insulin-loaded cationic liposomes have been developed and optimized for improved oral delivery. Liposomes were prepared cationic to improve insulin encapsulation. CS was selected as a mucoadhesive coat to prolong the system's residence and absorption. The performance of CS-coated liposomes compared with uncoated liposomes was examined in vitro, ex vivo, and in vivo in streptozotocin-induced diabetic mice. Free uncoated liposomes showed high positive zeta potential of +58.8 ± 2.2 mV that reduced (+29.9 ± 1.4 mV) after insulin encapsulation, confirming the obtained high entrapment efficiency of 87.5 ± 0.6%. CS-coated liposomes showed nanosize of 439.0 ± 12.3 nm and zeta potential of +60.5 ± 1.9 mV. In vitro insulin release was limited to 18.9 ± 0.35% in simulated gastric fluid, whereas in simulated intestinal fluid, 73.33 ± 0.68% was released after 48 h from CS-coated liposomes. Ex vivo intestinal mucoadhesion showed increased tissue residence of CS-coated liposomes compared with uncoated liposomes. A striking reduction in the glucose level was observed 1 h after oral administration of CS-coated liposomes and maintained up to 8 h (p <0.01 vs. insulin solution or uncoated liposomes) within the normal value 129.29 ± 3.15 mg/dL. In conclusion, CS-coated insulin-loaded cationic liposomes improved loading efficiency with promising prolonged pharmacological effect.