Comparison of the efficacy and safety of miconazole 50-mg mucoadhesive buccal tablets with miconazole 500-mg gel in the treatment of oropharyngeal candidiasis: a prospective, randomized, single-blind, multicenter, comparative, phase III trial in patients treated with radiotherapy for head and neck cancer

BACKGROUND: Topical antifungal treatments are recommended but rarely used as first-line therapy for oropharyngeal candidiasis (OPC) in patients with cancer. Miconazole Lauriad 50-mg mucoadhesive buccal tablet (MBT) Loramyc reportedly delivered rapid and prolonged, effective concentrations of miconazole in the mouth. The objective of the current study was to compare MBT with miconazole 500-mg oral gel (MOG) in patients with head and neck cancer. METHODS: Two hundred eighty-two patients with head and neck cancer received a 14-day treatment of either single-dose MBT or MOG administered in 4 divided doses. The primary endpoint was clinical success at Day 14, and secondary endpoints included clinical success at Day 7, clinical cure, improvement in clinical symptoms, mycologic cure, recurrence rate, and safety. RESULTS: The success rate was statistically not inferior (P < .0001) in the MBT population to the rate observed in the MOG group (56% vs 49%, respectively; P < .0001). After adjustment for the extent of lesions and salivary secretions, a trend toward superiority was observed in favor of MBT (P = .13), particularly among patients with multiple lesions (P = .013). Results for secondary endpoints were comparable to those observed for the primary endpoint. Compliance with MBT was excellent, and >80% of patients completed treatment. Both treatments were safe. CONCLUSIONS: The success rate of MBT Loramyc was significantly not inferior to that of MOG in the treatment of cancer patients with OPC; and, after adjusting for prognostic variables, it was more effective than MOG. MBT was well tolerated and, thus, may be recommended as first-line treatment in cancer patients who have OPC as an alternative to systemic antifungal agents. Society.     

Utilization of propranolol hydrochloride mucoadhesive invasomes as a locally acting contraceptive: in-vitro,ex-vivo,and in-vivo evaluation

It was found that propranolol hydrochloride (PNL), which is a beta-blocker used for hypertension treatment, has a potent spermicidal activity through local anesthetic activity or beta-blocking effect on sperm cells subsequently it could be used as a contraceptive remedy. This study aimed to entrap PNL into invasomes (INVs) and then formulate it as a locally acting contraceptive gel. PNL-loaded mucoadhesive INVs were prepared via the thin-film hydration technique. The D-optimal design was utilized to fabricate INVs employing lipid concentration (X₁), terpenes concentration (X₂), terpenes type (X₃), and chitosan concentration (X₄) as independent variables, while their impact was observed for entrapment efficiency percent (Y₁; EE%), particle size (Y₂; PS), zeta potential (Y₃; ZP), and amount of drug released after 6 h (Y₄; Q6h). Design Expert® was bestowed to nominate the desired formula. The selected INV was subjected to further studies and formulated into a mucoadhesive gel for ex-vivo and in-vivo investigations. The optimum INV showed a spherical shape with EE% of 65.01 ± 1.24%, PS of 243.75 ± 8.13 nm, PDI of 0.203 ± 0.01, ZP of 49.80 ± 0.42 mV, and Q6h of 53.16 ± 0.73%. Differential scanning calorimetry study asserted the capability of INVs to entrap PNL. Permeation studies confirmed the desired sustained effect of PNL-loaded INVs-gel compared to PNL-gel, INVs, and PNL solution. Sperm motility assay proved the potency of INVs-gel to inhibit sperm motility. Besides, the histopathological investigation verified the tolerability of the prepared INVs-gel. Taken together, the gained data justified the efficacy of PNL-loaded INVs-gel as a potential locally acting contraceptive.     

复方中药口腔粘膜粘附缓释膜的研究

目的为了增加粘膜粘附缓释膜剂的粘附力,延长制剂在口腔内的滞留时间及制剂中药物的释放速率以提高药效.方法以溃宁复方中药为模型药,通过对制剂辅料的成膜性,膜剂的粘附力、溶解(崩解)时间、体外释放速率及在口腔停留时间的测定,对不同处方进行筛选.结果聚乙烯醇的成膜性好于其他的成膜材料,成膜材料形成骨架不溶解,加入羧甲基纤维素钠及聚羧乙烯后膜剂的粘附力为464±28g,T50171.6±13.0min.结论聚乙烯醇(型号1750)与羧甲基纤维素钠及聚羧乙烯以3∶6∶1的比例制成的膜剂为最佳处方,其膜的粘附性及释放速率均增加.     

阴道黏膜给药系统的研究进展

目的:综述阴道黏膜给药系统的最新应用进展。方法:根据国内外发表的文献,对阴道黏膜给药系统的应用加以分析和讨论。结果:阴道黏膜给药安全、有效、能避免首关效应、渗透性能强,延长药物滞留时间,提高生物利用度,可以改善患者用药顺应性。结论:阴道黏膜给药系统已成为目前研究的热点,它是传统给药方式的补充,具有广阔的应用前景。     

Nose to brain microemulsion-based drug delivery system of rivastigmine: formulation and ex-vivo characterization

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder leading to irreversible loss of neurons, cognition and formation of abnormal protein aggregates. Rivastigmine, a reversible cholinesterase inhibitor used for the treatment of AD, undergoes extensive first-pass metabolism, thus limiting its absolute bioavailability to only 36% after 3-mg dose. Due to extreme aqueous solubility, rivastigmine shows poor penetration and lesser concentration in the brain thus requiring frequent oral dosing. This investigation was aimed to formulate microemulsion (ME) and mucoadhesive microemulsions (MMEs) of rivastigmine for nose to brain delivery and to compare percentage drug diffused for both systems using in-vitro and ex-vivo study. Rivastigmine-loaded ME and MMEs were prepared by titration method and characterized for drug content, globule size distribution, zeta potential, pH, viscosity and nasal ciliotoxicity study. Rivastigmine-loaded ME system containing 8% w/w Capmul MCM EP, 44% w/w Labrasol:Transcutol-P (1:1) and 48% w/w distilled water was formulated, whereas 0.3% w/w chitosan (CH) and cetyl trimethyl ammonium bromide (as mucoadhesive agents) were used to formulate MMEs, respectively. ME and MMEs formulations were transparent with drug content, globule size and zeta potential in the range of 98.59% to 99.43%, 53.8?nm to 55.4?nm and ?2.73?mV to 6.52?mV, respectively. MME containing 0.3% w/w CH followed Higuchi model (r²?=?0.9773) and showed highest diffusion coefficient. It was free from nasal ciliotoxicity and stable for three months. However, the potential of developed CH-based MME for nose to brain delivery of rivastigmine can only be established after in-vivo and biodistribution study.     

Formulation and evaluation of mucoadhesive buccal films of enalapril maleate

Enalapril maleate is used in the treatment of hypertension and angina pectoris. It shows low bioavailability due to high hepatic first pass metabolism. Hence the present work was undertaken to formulate mucoadhesive buccal films of enalapril maleate with an objective to improve therapeutic efficacy, patient compliance and the bioavailability. In the present study ten formulations of mucoadhesive drug delivery system of enalapril maleate were prepared as buccal films, by solvent casting technique. Sodium carboxymethylcellulose, hydroxylpropylmethylcellulose, hydroxyethylcellulose and polyvinyl pyrrolidone K-90 were used as mucoadhesive polymers. Prepared films were evaluated for their weight, thickness, surface pH, swelling index, drug content uniformity, in vitro residence time, folding endurance in vitro release and permeation studies. Films exhibited controlled release over more than 10 h in permeation studies. It was concluded that the films containing 20 mg of enalapril maleate in sodium carboxymethylcellulose 2% w/v and hydroxyethyl cellulose 2% w/v (formulation F5), showed good swelling, a convenient residence time and promising controlled drug release, thus can be selected for the development of buccal film for effective therapeutic uses.     

Mucoadhesive buccal film containing ornidazole and dexamethasone for oral ulcers: in vitro and in vivo studies

A bilayered mucoadhesive buccal film containing a combination of ornidazole (OD) and dexamethasone sodium phosphate (DEX) was prepared using solvent casting to treat oral ulcers. Films were systematically evaluated in vitro to obtain the optimum formulation. The therapeutic effects of these films were investigated in the rabbit oral ulcer model and the in vivo release of OD and DEX in the human oral cavity was also evaluated. The backing layer contained ethyl cellulose and an optimal mucoadhesive layer containing both OD and DEX was produced. Films from the optimum formulation were 0.427?±?0.015?mm thick, weighed 55.89?±?0.79?mg, and had a surface pH of 6.34?±?0.01. The drug content of the optimum formulation approximated the theoretical value with good uniformity (2.959?±?0.106?mg/cm² for OD and 0.877?±?0.031?mg/cm² for DEX). The formulation showed favorable swelling characteristics and both drugs were released at >95% after 4?h. Moreover, the compound film had a statistically significant effect on mucosal repair and reduced ulcer inflammation without stimulating the human oral mucosa. C_max of OD in saliva was 37.04?μg/ml and that of DEX was 9.737?μg/ml. Given promising therapeutic effects, the compound film developed here could become a local drug delivery device for treating oral ulcers.     

锡类散缓释贴膜对复发性阿弗他溃疡家兔肿瘤坏死因子-α、白细胞介素-1及白细胞介素-2的影响

目的建立复发性阿弗他溃疡（RAU）家兔动物模型,观察锡类散缓释贴膜对RAU家兔肿瘤坏死因子-α（TNF-α）、白细胞介素-1（IL-1）及白细胞介素-2（IL-2）的影响。方法将9只家兔脊柱两侧皮内注射家兔口腔黏膜抗原乳化液建立RAU家兔模型,造模后将RAU家兔随机分为3组,每组3只。空白模型组不给药;模型贴膜组,固定家兔口腔,将锡类散缓释贴膜敷至溃疡面上,每日1次;模型散剂组,固定家兔口腔,锡类散吹撒至溃疡面上,每4 h 1次,每日3次,用药后固定2 h。连续用药5 d,检测给药后RAU家兔炎性细胞因子TNF-α及IL-1、IL-2表达水平。结果实验动物注射家兔口腔黏膜蛋白后出现口腔黏膜溃疡,于最后1次注射10 d后口腔溃疡开始增多。模型贴膜组和模型散剂组炎性细胞因子TNF-α、IL-1及IL-2表达水平均低于空白模型组（P〈0.01）,且模型贴膜组低于模型散剂组（P〈0.05）。结论锡类散缓释贴膜及锡类散对RAU家兔具有治疗作用,其机制可能与减少炎性细胞因子的分泌有关。     

Preparation of fluconazole buccal tablet and influence of formulation expedients on its properties

The aim of present study was to prepare buccal tablets of fluconazole for oral candidiasis.The dosage forms were designed to release the drug above the minimum inhibitory concentration for prolonged period of time so as to reduce the frequency of administration and to overcome the side effects of systemic treatment.The buccal tablets were prepared by using Carbopol 71G and Noveon AA-1 by direct compression method.Microcry stalline cellulose was used as the filler and its effect was also studied.The prepared...