生物粘附性达那唑缓释栓剂的处方筛选与体外释放度考察

目的 :生物粘附性达那唑栓剂的处方筛选 ,并考察其体外释放规律。方法 :以羟丙甲基纤维素 (HPMC)为缓释材料 ,将等量聚乙二醇6000(PEG6000)和聚乙二醇600(PEG600)以熔融法制备含不同HPMC量的缓释栓剂 ,考察释放度与HPMC用量之间的关系。结果 :随着HPMC用量增加 ,栓剂释药减慢 ,当HPMC与PEG的比例为1∶6 5时 ,栓剂中药物在体外12h内缓慢释放 ,符合一级释放规律。结论 :生物粘附性骨架材料HPMC能延缓达那唑从栓剂中释放 ,当HPMC与PEG的比例为1∶6 5时栓剂能达到设计要求。     

乙酰螺旋霉素口腔贴片的研制及体外释药的考察

目的:研制乙酰螺旋霉素口腔贴片。方法:以卡波姆934P和HPMC(K4M)作为黏附材料,制备口腔贴片,并对其生物黏附力及体外释放度进行了考察,采用一阶导数光谱法测定乙酰螺旋霉素的含量。结果:卡波姆934P的生物黏附性优于HPMC,体外释放均符合Higuchi方程,HPMC的缓释效果优于卡波姆934P。结论:处方中以卡波姆934P与HPMC配比为1:1时为最优处方。     

盐酸丁螺环酮口腔粘附片的制备及释药机理初步研究

口腔粘附制剂是指将药物与适宜的生物粘附剂等辅料经加工制成的制剂 ,使用时将制剂粘附于口腔粘膜上 ,恒定释放药物。口腔粘附制剂不仅能够局部治疗口腔疾病 ,而且药物可以透过口腔粘膜吸收 ,进入血液循环 ,起到全身治疗作用。药物经口腔粘膜吸收时 ,避免了胃肠道及肝脏的首过作用 ,因此对于易受胃肠道酸和酶降解的蛋白质、肽类及其他大分子药物 ,以及受肝脏首过代谢作用严重的药物 ,通过口腔粘膜给药可以提高生物利用度[1] 。本文选择的药物盐酸丁螺环酮 (ｂｕｓｐｉｒｏｎｅｈｙｄｒｏｃｈｌｏｒｉｄｅ)是一个新型的非苯二氮类抗焦虑症…     

冬凌草甲素纳米结晶黏附性缓释片的制备及体外评价

目的制备冬凌草甲素纳米结晶黏附片,考察其体外释放性、黏附性和结晶药物形态。方法采用高压均质法将冬凌草甲素制成纳米结晶,以羟丙甲纤维素(HPMC)和卡波姆为生物黏附材料,甘露醇为稀释剂和支架剂制备冬凌草纳米结晶生物黏附性缓释片。采用紫外分光光度法测定冬凌草甲素的含量,采用正交设计结合多元线性回归,以累计释放率为主要考察指标,考察了HPMC、卡波姆、甘露醇的用量对药物溶出的影响,确定了片剂的优化处方,并对片剂的黏附性和体外药物释放做了考察。结果最佳处方含HPMC31.0%,卡波姆21.7%,甘露醇7.44%。片剂中药物以纳米结晶形式从片剂中溶出,而且具有黏附和缓释作用。结论以最佳制备工艺条件制备纳米结晶片,制备工艺简单,重现性好。同时体外实验表明,冬凌草甲素纳米结晶生物黏附性缓释片显示了纳米结晶与生物黏附的双重优点。     

Effect of formulation variables on drug and polymer release from HPMC-based matrix tablets

The objective of this work was to assess the effect of two formulation variables, hydroxypropylmethylcellulose (HPMC)/lactose ratio and HPMC viscosity grade, on the release of a model drug and HPMC, as well as the mechanism of drug release from HPMC-based matrix tablets. A water-soluble compound, adinazolam mesylate, was used as the model drug. Both drug and HPMC release were found to be a function of the formulation variables, with higher drug and HPMC release rates for formulations with lower HPMC/lactose ratios and lower HPMC viscosity grades. However, the K15M and K100M formulations had identical drug release profiles. All the drug release data fit well to the Higuchi expression. By comparing the drug and HPMC release data, it was concluded that diffusion of drug through the hydrated gel layer was the predominant drug release mechanism for most of the formulations studied.     

中心复合设计法优化维生素C阴道生物黏附缓释片处方

目的：制备维生素C阴道生物黏附缓释片,考察其释放和黏附性能的影响因素,并运用中心复合设计法优化处方。方法：选用羟丙甲纤维素和卡波普分别作为骨架材料及生物黏附材料制备缓释片,采用自制装置测定缓释片的生物黏附力,应用相似因子法评价不同处方工艺制备的缓释片释放行为;以缓释片的生物黏附力和释放度综合评分为评价指标,对羟丙甲纤维素和卡波普的用量进行多元线性回归和二项式拟合,预测最优处方。结果：经预测分析,获得最优处方,且由此优化处方制备的缓释片各评价指标的实验值与预测值很接近。结论：应用中心复合设计法优化维生素C阴道生物黏附缓释片处方,切实可行。     

小檗碱生物黏附缓释片的制备及体外评价

目的 测定小檗碱生物黏附缓释片和大鼠离体胃组织的黏附力,探究其体外释药作用,制备小檗碱生物黏附缓释片。方法 以羟丙基甲基纤维素(HPMC)和卡波姆(carbopol,CP)为生物黏附材料,通过正交试验对辅料用量进行优化。测定生物黏附缓释片的释放度,溶出介质为人工胃液(pH=1.2)。通过自制黏附力测定装置测定、比较小檗碱生物黏附缓释片和盐酸小檗碱片对大鼠离体胃组织的黏附力。结果 每片生物黏附缓释片中974P/971P为1/3,卡波姆用量为20 mg,羟丙基甲基纤维素为15 mg。生物黏附缓释片的体外释放达到缓释制剂要求,与普通片剂相比其对大鼠离体胃组织的黏附力更大。结论 小檗碱生物黏附缓释片的处方和工艺能够达到设计要求。     

Effect of HPMC and mannitol on drug release and bioadhesion behavior of buccal discs of buspirone hydrochloride: In-vitro and in-vivo pharmacokinetic studies

Delivery of orally compromised therapeutic drug molecules to the systemic circulation via buccal route has gained a significant interest in recent past. Bioadhesive polymers play a major role in designing such buccal dosage forms, as they help in adhesion of designed delivery system to mucosal membrane and also prolong release of drug from delivery system. In the present study, HPMC (release retarding polymer) and mannitol (diluent and pore former) were used to prepare bioadhesive and controlled release buccal discs of buspirone hydrochloride (BS) by direct compression method. Compatibility of BS with various excipients used during the study was assessed using DSC and FTIR techniques. Effect of mannitol and HPMC on drug release and bioadhesive strength was studied using a 3² factorial design. The drug release rate from delivery system decreased with increasing levels of HPMC in formulations. However, bioadhesive strength of formulations increased with increasing proportion of HPMC in buccal discs. Increased levels of mannitol resulted in faster rate of drug release and rapid in vitro uptake of water due to the formation of channels in the matrix. Pharmacokinetic studies of designed bioadhesive buccal discs in rabbits demonstrated a 10-fold increase in bioavailability in comparison with oral bioavailability of buspirone reported.     

Development and evaluation of a buccal bioadhesive system for smoking cessation therapy

The objective of the present study was to develop a bilayered buccal bioadhesive film formulation of nicotine hydrogen tartrate for smoking cessation therapy, comprising a bioadhesive drug layer and a backing layer, which releases the drug at a pre-determined rate for a period of 4 h. Formulations were prepared using various bioadhesive polymers and were evaluated for physical parameters like peelability, flexibility, softness, bioadhesive strength, tensile strength, dispersion time and pharmaceutical parameters such as thickness, swelling, content uniformity, water vapour permeability and drug release. Based on these parameters formulation N2, containing hydroxypropyl methylcellulose and polycarbophil as the bioadhesive polymers, was selected as the optimized formulation. The formulation showed suitable adhesion and an initial burst release of 40% drug in first 15 min followed by a total 80% drug release in a characteristic manner until 4 h; which is the desired time of application. This release pattern is beneficial for patients suffering from emergent cravings. Backing layers of the films were studied by a moisture vapor permeability test and it was observed that the percentage of moisture which permeated through single layered films was much higher than through bilayered films implying that a backing layer would prevent washing out of drug by the saliva.     

咪康唑颊贴缓释片的黏附性能测试方法的建立及处方优化

目的建立咪康唑颊贴缓释片的黏附性能测试方法并优化处方。方法采用自制黏附力测定装置,运用正交试验法,考察乳蛋白和卡波姆974的比例,乳蛋白和卡波姆974的总量,HPMC的用量三个主要影响因素,对咪康唑颊贴缓释片的黏附力和溶胀速率的影响。结果当乳蛋白∶卡波姆974=2∶1,乳蛋白和卡波姆974总量为30 mg,HPMC的量为20 mg时,咪康唑颊贴片的黏附性能最好,可以满足口腔颊贴缓释片的要求。结论自制的黏附力测定装置可以用于咪康唑颊贴缓释片的黏附性能测试。     

Evaluation of bioadhesive buccal tablets containing triamcinolone acetonide in healthy volunteers

The behaviour of bioadhesive buccal tablets prepared from different ratios of poly(acrylic acid-2,5-dimethyl-1,5-hexadiene) (PADH) and hydroxypropylmethylcellulose (HPMC) with and without triamcinolone acetonide (TAA) has been investigated in the buccal cavities of healthy human volunteers. The results indicate that tablets with a higher ratio of PADH swell faster, causing the disintegration of the tablets and consequently give rise to more rapid release of drug. The inclusion of higher percentages of HPMC provides more prolonged release of drug through its properties of gelling and slow dissolution. However, adhesion of the tablet is reduced in the excessive flow of saliva and there is also a tendency for the tablet to be dislodged from the mucosa. The tablet with a PADH/HPMC ratio of 50:50 seems to provide a suitable compromise for good bioadhesion and prolonged release of drug.     

In vivo bioavailability studies of sumatriptan succinate buccal tablets

Back ground and the purpose of study

Sumatriptan succinate is a Serotonin 5- HT1 receptor agonist, used in treatment of migraine. It is absorbed rapidly but incompletely when given orally and undergoes first-pass metabolism, resulting in a low absolute bioavailability of about 15%. The aim of this work was to design mucoadhesive bilayered buccal tablets of sumatriptan succinate to improve its bioavailability.

Methods

Mucoadhesive polymers carbopol 934 (Carbopol), HPMC K4M, HPMC K15M along with ethyl cellulose as an impermeable backing layer were used for the preparation of mucoadhesive bilayered tablets. In vivo bioavailability studies was also conducted in rabbits for optimized formulation using oral solution of sumatriptan succinate as standard.

Results

Bilayered buccal tablets (BBT) containing the mixture of Carbopol and HPMC K4M in the ratio 1:1 (T1) had the maximum percentage of in vitro drug release within 6 hrs. The optimized formulation (T1) followed non-Fickian release mechanism. The percentage relative bioavailability of sumatriptan succinate from selected bilayered buccal tablets (T1) was found to be 140.78%.

Conclusions

Bilayered buccal tablets of sumatriptan succinate was successfully prepared with improved bioavailability.     

Development and in vitro evaluation of buccoadhesive carvedilol tablets

Buccoadhesive tablets of carvedilol were prepared using HPMC K4M, HPMC K15M and Carbopol 934 as mucoadhesive polymers. Fifteen formulations were developed with varying concentrations of polymers. Formulations of the BC or BD series were composed of HPMC K4M or HPMC K15M in ratios of 1:1 to 1:5 whereas in the BE series Carbopol 934 was used (1:0.25 to 1:1.50). The formulations were tested for in vitro drug release, in vitro bioadhesion, moisture absorption and in vitro drug permeation through porcine buccal mucosa. Formulation BC3 showed maximum release of the drug (88.7 +/- 0.4%) with the Higuchi model release profile and permeated 21.5 +/- 2.9% of the drug (flux 8.35 +/- 0.291 microg h(-1)cm(-2)) permeation coefficient 1.34 +/- 0.05 cm h(-1)) through porcine buccal membrane. BC3 formulation showed 1.62 +/- 0.15 N of peak detachment force and 0.24 +/- 0.11 mJ of work of adhesion. FTIR results showed no evidence of interaction between the drug and polymers. XRD study revealed that the drug is in crystalline form in the polymer matrix. The results indicate that suitable bioadhesive buccal tablets with desired permeability could be prepared.     

Optimization of propranolol HCl release kinetics from press coated sustained release tablets

Press-coated sustained release tablets offer a valuable, cheap and easy manufacture alternative to the highly expensive, multi-step manufacture and filling of coated beads. In this study, propranolol HCl press-coated tablets were prepared using hydroxylpropylmethylcellulose (HPMC) as tablet coating material together with carbopol 971P and compressol as release modifiers. The prepared formulations were optimized for zero-order release using artificial neural network program (INForm, Intelligensys Ltd, North Yorkshire, UK). Typical zero-order release kinetics with extended release profile for more than 12 h was obtained. The most important variables considered by the program in optimizing formulations were type and proportion of polymer mixture in the coat layer and distribution ratio of drug between core and coat. The key elements found were; incorporation of 31–38 % of the drug in the coat, fixing the amount of polymer in coat to be not less than 50 % of coat layer. Optimum zero-order release kinetics (linear regression r2 = 0.997 and Peppas model n value > 0.80) were obtained when 2.5–10 % carbopol and 25–42.5% compressol were incorporated into the 50 % HPMC coat layer.     

Development of a buccal bioadhesive nicotine tablet formulation for smoking cessation

Bioadhesive buccal tablet formulations for delivery of nicotine into the oral cavity were developed. Carbomer (Carbopol)974P NF) (CP) and alginic acid sodium salt (NaAlg) were used as bioadhesive polymers in combination with hydroxypropyl methylcellulose (HPMC) at different ratios. Magnesium carbonate was incorporated into the formulations as a pH increasing agent. In vitro release and bioadhesion studies were performed on the developed tablets. In the formulations containing CP:HPMC, the NHT released increased with the increasing HPMC concentration whereas a decrease was observed with increasing HPMC concentration in formulations containing NaAlg:HPMC. The bioadhesive properties of the tablets containing NaAlg:HPMC was not affected by the concentration of the NaAlg (P>0.05) but increased significantly with the increasing CP concentration (P>0.05). A decrease in pH of the dissolution medium to acidic values was avoided by incorporation of magnesium hydroxide into the formulations. The developed formulations released NHT for 8h period, and remained intact except for the formulation containing CP:HPMC at 20:80 ratio.     

Formulation and evaluation of mucoadhesive buccal films impregnated with carvedilol nanosuspension: a potential approach for delivery of drugs having high first-pass metabolism

Abstract

Context: Mucoadhesive buccal films containing three layers (mucoadhesive layer, nanosuspension containing layer and backing membrane) were incorporated with carvedilol nanosuspension.

Objective: Formulation and evaluation of nanosuspension incorporated mucoadhesive buccal films of carvedilol for bioavailability enhancement by avoiding first-pass metabolism.

Methods: Carvedilol-loaded nanosuspension was prepared by a precipitation–ultrasonication method with varying concentrations of the polymer. The formulation was analyzed for size, size distribution, surface charge and morphology. Optimized nanosuspension was incorporated into drug gel layer which was sandwiched between a mucoadhesive layer and a backing layer to form tri-layered buccal films. They were evaluated for their physical, mechanical and bioadhesive parameters followed by in vitro and in vivo studies.

Results and discussion: Nanosuspension showed a negative zeta potential (?17.21?mV) with a diameter of around 495 nm and a polydispersity index of 0.203. Nanosuspension incorporated drug gel layer (62.4% drug loading) was optimized to contain 3% HPMC and 50?mg Carbopol 934P. The mucoadhesive layer and the backing layer were optimized to contain 3% HPMC and 1% ethyl cellulose, respectively. In vitro drug release was 69% and 62.4% in 9?h across synthetic membrane and porcine buccal mucosa, respectively. In vivo studies conducted in rabbit model showed 916% increase in the relative bioavailability in comparison to marketed oral tablet formulation. The C_max and T_max of the prepared formulation increased due to increased surface area of drug and also by-passing hepatic metabolism.

Conclusion: The drug delivery system has been designed as a novel platform for potential buccal delivery of drugs having high first-pass metabolism.     

Benzydamine hydrochloride buccal bioadhesive gels designed for oral ulcers: Preparation,rheological, textural,mucoadhesive and release properties

This study developed and examined the characterization of Benzidamine hydrochloride (BNZ) bioadhesive gels as platforms for oral ulcer treatments. Bioadhesive gels were prepared with four different hydroxypropylmethylcellulose (HPMC) types (E5, E15, E50 and K100M) with different ratios. Each formulation was characterized in terms of drug release, rheological, mechanical properties and adhesion to a buccal bovine mucosa. Drug release was significantly decreased as the concentration and individual viscosity of each polymeric component increased due to improved viscosity of the gel formulations. The amount of drug released for the formulations ranged from 0.76?±?0.07 and 1.14?±?0.01 (mg/cm²?±?SD). Formulations exhibited pseudoplastic flow and all formulations, increasing the concentration of HPMC content significantly raised storage modulus (G′), loss modulus (G″), dynamic viscosity (?′) at 37°C. Increasing concentration of each polymeric component also significantly improved the hardness, compressibility, adhesiveness, cohesiveness and mucoadhesion but decreased the elasticity of the gel formulations. All formulations showed non-Fickian diffusion due to the relaxation and swelling of the polymers with water. In conclusion, the formulations studied showed a wide range of mechanical and drug diffusion characteristics. On the basis of the obtained data, the bioadhesive gel formulation which was prepared with 2.5% HPMC K 100M was determined as the most appropriate formulation for buccal application in means of possessing suitable mechanical properties, exhibiting high cohesion and bioadhesion.     

Design of a dissolution apparatus suitable for in situ release study of triamcinolone acetonide from bioadhesive buccal tablets

A new and simple dissolution apparatus which is capable of evaluating the release of drug and bioadhesive properties of buccal tablets has been developed. The apparatus consists of a dissolution cell and an outer assembly. The cell has been designed to hold the chicken pouch membrane and bioadhesive tablet together and also to allow the dissolution medium to flow over them. The outer assembly is to provide adjustment of the angle of flow of the medium over the cell. The release study of triamcinolone acetonide from various bioadhesive buccal tablets containing different proportions of poly(acrylic acid-2.5-dimethyl-1,5-hexadiene) (PADH) and hydroxypropylmethyl-cellulose (HPMC) with the apparatus reveals that the bioadhesion of the tablet and the release of drug are influenced by the different proportions of polymers. With higher concentrations of PADH, the tablets disintegrate much more rapidly, leading to a faster release of the drug and they give better adhesion to the membrane. Tablets with higher concentrations of HPMC provide more prolonged release of the drug. However, they can be dislodged from the membrane more easily. The results produced by the apparatus concur with the predicted patterns.     

Controlled release effervescent buccal discs of buspirone hydrochloride: in vitro and in vivo evaluation studies

Abstract

In the present study controlled release effervescent buccal discs of buspirone hydrochloride (BS) were designed using HPMC as rate controlling and bioadhesive polymer by direct compression method. Sodium bicarbonate and citric acid were used in varying amounts as effervescence forming agents. Carbon dioxide evolved due to reaction of sodium bicarbonate and citric acid was explored for its potential as buccal permeation enhancer. The designed buccal discs were evaluated for physical characteristics and in vitro drug release studies. Bioadhesive behavior of designed buccal discs was assessed using texture analyzer. In vivo animal studies were performed in rabbits to study bioavailability of BS in the designed buccal discs and to establish permeation enhancement ability of carbon dioxide. It was observed that effervescent buccal discs have faster drug release compared to non-effervescent buccal discs in vitro and effervescent buccal discs demonstrated significant increase in bioavailability of drug when compared to non-effervescent formulation. Hence, effervescent buccal discs can be used as an alternative to improve the drug permeation resulting in better bioavailability. However, the amount of acid and base used for generation of carbon dioxide should be selected with care as this may damage the integrity of bioadhesive dosage form.     

大蒜油口腔黏附片的研究

目的 研制大蒜油口腔黏附片,并考察其生物黏附性及释药性能.方法 采用羟丙基甲基纤维素(HPMC)和卡波姆(Carbopol 934P)为黏附材料,制备不同处方配比的大蒜油口腔黏附片,测定其体外溶胀百分率、黏附力和黏附时间,并采用浆法测定释放度.结果 以HPMC: Carbopol 934P为3:1的处方制得的口腔黏附片较好.结论 成功制备了大蒜油口腔黏附片.