盐酸帕洛诺司琼在健康人体的药动学研究

目的：研究盐酸帕洛诺司琼注射液在健康志愿者体内的药动学。方法：24名健康志愿者按随机数字表法分成3组,每组8人,男女不限,分别单剂量静脉注射0.25、0.50和0.75mg 3种剂量的盐酸帕洛诺司琼注射液后,采用HPLC-MS/MS法测定人血浆中帕洛诺司琼的浓度,用DAS 2.0软件计算药动学参数。结果：3组受试者的主要药动学参数如下：cmax（5.57±2.97）、（6.84±5.48）和（9.75±5.78）μg/L;AUC0～t（24.3±7.6）、（48.3±14.6）和（74.7±25.4）μg.h.L-1;t1/2β（31.0±5.6）、（33.5±5.6）和（31.1±5.0）h。结论：在0.25～0.75mg剂量范围内帕洛诺司琼在健康志愿者体内呈线性药动学特征。本研究建立的帕洛诺司琼测定方法灵敏、准确、简便。     

帕洛诺司琼联合地塞米松预防甲状腺切除术后恶心、呕吐

目的观察帕洛诺司琼联合地塞米松对甲状腺切除术患者术后恶心呕吐的预防作用。方法 120例行甲状腺切除术患者随机分为联合组、帕洛诺司琼组、对照组,预计手术结束前30 min,对照组静脉注射生理盐水2 mL,帕洛诺司琼组静脉注射帕洛诺司琼0.25 mg,联合组静脉注射帕洛诺司琼0.25 mg和地塞米松10 mg。观察三组术后24 h发生恶心呕吐情况并作比较。结果联合组恶心呕吐的发生率明显优于对照组(P<0.05)。结论帕洛诺司琼联合地塞米松可降低甲状腺切除患者术后恶心呕吐发生率。     

盐酸帕洛诺司琼注射液在健康人体内的药动学研究

目的研究盐酸帕洛诺司琼注射液在健康受试者体内的药动学过程。方法36名健康志愿者随机分成3组,每组12人,男女各半,分别单剂量静脉注射盐酸帕洛诺司琼0．25、0．5和0．75mg,血浆中帕洛诺司琼浓度用HPLC-MS／MS法测定,以DAS2．1．1软件计算药动学参数。结果单剂量静脉注射盐酸帕洛诺司琼注射液0．25、0．5和0．75mg后主要药动学参数如下：t1/2分别为（43．9±10．7）、（44.3±9．8）、（43．2±13．5）h,Cmax分别为（4．18±2．35）、（8．80±6．83）、（12．7±11．3）μg·L^-1,AUC0～t分别为（37．9±11．1）、（69．9±22．5）、（108．4±40．3）μg·h·L^-1,AUC0～∞分别为（41．6±12．2）、（74．8±24．1）、（117．7±48．1）μg·h·L^-1,CL分别为（6．6±2．1）、（7．5±2．9）、（7．3±2．7）L·h^-1。结论中国健康受试者单剂量静脉注射盐酸帕洛诺司琼后,在0.25～0．75mg剂量呈线性药动学特征,本试验建立的测定方法简便、灵敏、准确。     

双氯芬酸钠贴片的制备及体外释放、透皮吸收测定分析

目的探讨双氯芬酸钠贴片的制备方法,分析其体外释放与透皮吸收能力。方法制备以聚丙烯酸酯为骨架的双氯芬酸钠贴片,进行体外透皮与释放度试验、制备DCF标准曲线、进行DCF贴片释放度试验,用蛇皮进行体外经皮渗透试验,以改进Franz扩散池检验药物的经皮渗透性能。结果成功制作了以聚丙烯酸酯为骨架的双氯芬酸钠贴片,测定显示,双氯芬酸钠贴片的体外释放速率为21.98μg/(cm2 h1/2),体外透皮速率为17.97μg/(cm2 h1/2)。结论本次研究制定的双氯芬酸钠贴片的释放度曲线与24h累计渗透量与Higuchi方程相符合,是一种新型的缓释型外用制剂。     

盐酸帕洛诺司琼胶囊的人体药动学及绝对生物利用度

目的:研究盐酸帕洛诺司琼胶囊在健康受试者体内的药动学及绝对生物利用度。方法:24例健康受试者(男12,女12),平均分为2组,按自身双交叉试验设计。一组分别单剂量口服低、高(0.25,0.75 mg)剂量;另一组分别单剂量口服和静脉注射中剂量(0.5 mg)。给药后0～168 h间隔取血。采用液相色谱-串联质谱法(LC-MS/MS)测定血浆帕洛诺司琼浓度,应用DAS 2.1程序计算药动学参数并评价口服制剂的绝对生物利用度。结果:单剂量口服0.25和0.75 mg盐酸帕洛诺司琼胶囊后的主要药动学参数Cmax分别为(0.58±0.20)和(1.95±0.94)ng.mL-1,Tmax分别为(8.4±3.9)和(8.3±2.9)h,AUC0～168分别为(35±10)和(82±34)h.ng.mL-1,t1/2分别为(74±18)和(41±9)h;单剂量0.5 mg口服与静脉注射后的主要药动学参数Cmax分别为(0.82±0.17)和(5.58±2.66)ng.mL-1,Tmax分别为(6.3±4.3)和(0.022±0.019)h,AUC0～168分别为(43±12)和(40±12)h.ng.mL-1,t1/2分别为(44±9)和(54±18)h。由AUC0～168估算,口服胶囊的绝对生物利用度为(109.9±26.1)%。结论:在0.25～0.75 mg剂量范围内口服盐酸帕洛诺司琼胶囊具有线性药动学特征;口服生物利用度较高,但是与静脉注射相比,口服给药的Cmax明显降低,Tmax显著延迟;主要药动学参数性别间无差异。     

帕洛诺司琼治疗化疗呕吐的临床研究进展

帕洛诺司琼是第一个获准用于预防迟发性化疗所致恶心、呕吐（chemotherapy-induced nausea and vomiting,CINV）的5-羟色胺3（5-HT3）受体拮抗剂。通过比较,发现帕洛诺司琼治疗急性期CINV至少同第一代5-HT3受体拮抗剂同样有效,对延迟性CINV的疗效优于第一代5-HT3受体拮抗剂。本文综述了帕洛诺司琼的临床研究进展,并探讨了多剂量给予帕洛诺司琼的安全性和有效性。     

药学干预对临床帕洛诺司琼止吐预防性使用的影响

目的:探讨临床药师的药学干预对帕洛诺司琼止吐预防性使用的影响。方法:设计一项前后测试的准实验,由一名专职临床药师主导药学干预过程。考察指标包括帕洛诺司琼止吐预防性使用的处方合格率、止吐方案与指南(专家共识)的一致性、不良反应发生率、呕吐完全缓解率及帕洛诺司琼预防呕吐的平均费用。在药学干预结束后半年内,继续考察,以评估药学干预作用有无延续性。结果:与对照组相比,干预组帕洛诺司琼止吐预防性使用的处方合格率、止吐方案与指南(专家共识)的一致性均由11%提高至56%(P<0.01),不良反应发生率由26%减少至14%(P=0.034),呕吐完全缓解率由100%降至96%(P=0.043),帕洛诺司琼预防呕吐的平均费用由815元/例降至591.5元/例(P=0.014)。对术后恶心呕吐组与化疗相关性恶心呕吐组分别进行亚组分析,经过药学干预,帕洛诺司琼预防术后恶心呕吐的安全性、经济性得到提高,有效性同干预前。帕洛诺司琼预防化疗相关性恶心呕吐的安全性、经济性同干预前,有效性虽降低,但仍高达94.74%(P=0.043)。干预后组与干预组比较,相关指标无显著性差异(P>0.05)。结论:药学干预对促进帕洛诺司琼临床合理使用,增强临床循证行为,具有积极作用,且干预作用具延续性。     

盐酸帕洛诺司琼对比格拉司琼在老年急性髓系白血病化疗相关恶心和呕吐的临床研究

目的比较盐酸帕洛诺司琼与格拉司琼在老年急性髓系白血病(AML)化疗相关恶心呕吐(CINV)反应治疗效果。方法将符合纳入标准的老年AML患者24例,按随机数字表法分为试验组和对照组,每组各12例,试验组采用盐酸帕洛诺司琼注射液预防呕吐,对照组使用格拉司琼治疗,观察2组患者化疗期间及化疗后第1～5天的恶心、呕吐、食欲以及全身情况。结果帕洛诺司琼对比格拉司琼预防化疗过程中及化疗后急性CINV控制有效率分别为92%和83%,在治疗后48 h迟发性CINV的有效率分别是92%和83%,2组间比较差异有统计学意义(P<0.05);盐酸帕洛诺司琼在迟发性呕吐分层缓解率高于格拉司琼,2种药物均有轻微疲乏、便秘、头晕、头痛等不良反应。结论在老年AML化疗中,帕洛诺司琼对于预防CINV的疗效优于格拉司琼,不良反应发生率低、程度轻。     

不同剂量帕洛诺司琼对微创胆囊切除术后预防恶心呕吐的疗效比较

目的:比较不同剂量帕洛诺司琼对微创胆囊切除术后预防恶心呕吐的临床疗效。方法:选取2015年1—12月间收治的全身麻醉下行腹腔镜胆囊切除术患者90例,将其分为Ⅰ组(30例)、Ⅱ组(30例)和Ⅲ组(30例);Ⅰ组患者给予帕洛诺司琼0.25 mg,Ⅱ组患者给予帕洛诺司琼0.5 mg,Ⅲ组患者给予帕洛司琼0.75 mg;比较3组患者麻醉诱导前静脉推注帕洛诺司琼注射液不同剂量后,不同时段(0~3 h、3~24 h、24~48 h和48~72 h)内恶心呕吐的发生情况以及完全缓解率(complete response rate,CRR)。结果:3组患者在0~3 h、3~24 h和24~48 h时间段内恶心呕吐症状明显缓解;Ⅲ组患者在各时间段内恶心呕吐的发生率明显低于Ⅰ组和Ⅱ组(P<0.05);Ⅱ组患者恶心呕吐的发生率明显低于Ⅰ组(P<0.05);在前3个时间段内,Ⅱ组与Ⅰ组比较,完全缓解率较高,差异比较有统计学意义(P<0.05);在前3个时间段内,Ⅲ组患者的完全缓解率明显高于Ⅰ组和Ⅱ组(P<0.05)。结论:采用静脉推注0.5 mg帕洛诺司琼可有效预防微创胆囊切除术后的恶心呕吐,其疗效优于0.25 mg和0.75 mg帕洛诺司琼。     

盐酸帕洛诺司琼注射液的制备和质量控制

目的:制备盐酸帕洛诺司琼注射液,并建立质量控制方法。方法:考察辅料用量、配伍液和灭菌参数等对制剂的影响,参照盐酸帕洛诺司琼注射液同类产品Aloxi的处方,确定制剂处方工艺。采用HPLC法,测定制剂中盐酸帕洛诺司琼的含量和有关物质,并考察制剂稳定性。结果:金属络合剂依地酸二钠、渗透压调节剂甘露醇和针用活性炭的用量分别为盐酸帕洛诺司琼注射液制剂体积的0.01%、4.15%和0.01%(质量浓度分别为0.1、41.5和0.1 g.L-1);制剂与0.9%氯化钠注射液和5%葡萄糖注射液配伍时含量不受影响;流通蒸汽灭菌条件为121℃下15 min。制备的盐酸帕洛诺司琼注射液含量和有关物质以及稳定性均符合质量控制要求。HPLC法所测盐酸帕洛诺司琼质量浓度的线性范围为1～200 mg.L-1(r2=0.999 7)。结论:该处方工艺合理、实用,质量控制方法可靠、易行。     

Design,development, physicochemical,in vitro and in vivo evaluation of monolithic matrix type transdermal patches containing nitrendipine

The matrix type transdermal drug delivery systems (patches) of Nitrendipine were prepared by film casting technique. The patches were characterized for physical, in vitro release studies and ex-vivo permeation studies (human cadaver skin). On the basis of in vitro drug release and skin permeation performance, formulation B3 was found to be better than the other formulations and it was selected as the optimized formulation. The final optimized formulation (B3) was subjected to skin irritation, pharmacokinetic, pharmacodynamic and stability studies. The maximum percentage drug release in 48 hours was 94.67 ± 3.25 for B3 and 91.43 ± 2.106 for A2 formulation. Again formulation B3 (0.0627 mg/cm²/h) and A2 (0.0566 mg/cm²/h) showed maximum skin flux in the respective series. Patches prepared with Plasdone S-630 were more flexible as compared to PVP K 30 containing patches. Patches prepared with PVP K 30 showed drug release and skin permeation at higher percentage as compared to those containing Plasdone S-630. The interaction studies carried out by comparing the results of ultraviolet, infrared, TLC and DSC analyses for the pure drug, medicated and placebo formulations indicated no chemical interaction between the drug and excipients. The TDDS was found to be free of any skin irritation as suggested by skin irritation score of 1.16 (< 2.00) under Draize score test.     

Design,development, physicochemical,and in vitro and in vivo evaluation of transdermal patches containing diclofenac diethylammonium salt

In this study, matrix-type transdermal patches containing diclofenac diethylamine were prepared using different ratios of polyvinylpyrrolidone (PVP) and ethylcellulose (EC) by solvent evaporation technique. The drug matrix film of PVP and EC was casted on a polyvinylalcohol backing membrane. All the prepared formulations were subjected to physical studies (moisture content, moisture uptake, and flatness), in vitro release studies and in vitro skin permeation studies. In vitro permeation studies were performed across cadaver skin using a modified diffusion cell. Variations in drug release profiles among the formulations studied were observed. Based on a physicochemical and in vitro skin permeation study, formulation PA4 (PVP/EC, 1:2) and PA5 (PVP/EC, 1:5) were chosen for further in vivo experiments. The antiinflammatory effect and a sustaining action of diclofenac diethylamine from the two transdermal patches selected were studied by inducing paw edema in rats with 1% w/v carrageenan solution. When the patches were applied half an hour before the subplantar injection of carrageenan in the hind paw of male Wistar rats, it was observed that formulation PA4 produced 100% inhibition of paw edema in rats 12 h after carrageenan insult, whereas in the case of formulation PA5, 4% mean paw edema was obtained half an hour after the carrageenan injection and the value became 19.23% 12 h after the carrageenan insult. The efficacy of transdermal patches was also compared with the marketed Voveran gel and it was found that PA4 transdermal patches produced a better result as compared with the Voveran gel. Hence, it can be reasonably concluded that diclofenac diethylamine can be formulated into the transdermal matrix type patches to sustain its release characteristics and the polymeric composition (PVP/EC, 1:2) was found to be the best choice for manufacturing transdermal patches of diclofenac diethylamine among the formulations studied.     

Novel biomaterial for transdermal application: in vitro and in vivo characterization

The objective of the present study was to evaluate a novel film forming biomaterial for its potential application in the preparation of unilaminate transdermal adhesive matrix systems. The biomaterial, Damar Batu (DB), was tried alone and in combination with Eudragit RL100 as a matrixing agent in the preparation of transdermal patches. Developed transdermal patches of Diltiazem hydrochloride (DH) were evaluated for thickness uniformity, weight uniformity, folding endurance and drug content. USP dissolution apparatus V was used for in vitro drug release studies. Modified Franz diffusion cell used for permeation study using excised human cadaver skin. Total 6 formulations were developed and on the basis of in vitro drug release and in vitro skin permeation profile F5 composed of DB: Eudragit RL100 (60:40) and carrying 20 %w/w DH was selected as an optimized formulation for in vivo study. The in vivo study results showed that F5 achieved the Cmax of about 269.76 ± 1.52 ng/mL in 6 h and sustained the release of the drug till 24 h. The skin irritation study results proved that the novel biomaterial is non-sensitizing and non-irritating. Drug-polymer interaction study carried out to check the compatibility of drug and polymer showed the intactness of the drug in the formulation proving the compatibility of the polymer. It can be proposed from the outcome of the present study that by applying suitable adhesive layer and backing membrane, DB: Eudragit RL100 (60:40) transdermal patches can be of potential therapeutic use.     

Ketotifen Fumarate and Salbutamol Sulphate Combined Transdermal Patch Formulations: In vitro release and Ex vivo Permeation Studies

The present work was performed to develop and evaluate transdermal patches of combined antiasthmatic drugs (salbutamol sulphate and ketotifen fumarate). Polyvinyl alcohol membrane was used as backing membrane and eudragit RL-100 was used as matrix material to suspend the drugs in the continuous thickness of the patch. Methanol was solvent and propylene glycol was used as plasticizer. Tween 20, isopropyl myristate, eucalyptus oil, castor oil and span-20 were used as permeability enhancers. Thickness, weight variation and drug uniformity were investigated. The patch formulations were also subjected to drug release in dissolution media and permeation through rabbit skin. Effects of different enhancers were evaluated on release and permeation of drugs. F3 formulations having isopropyl myristate as permeation enhancer, showed maximum amounts of drugs release (88.11% of salbutamol sulphate and 88.33% of ketotifen fumarate) at the end of 24 h dissolution study. F3 also showed maximum permeation of both drugs (4.235 mg salbutamol sulphate and 1.057 mg ketotifen fumarate) after 24 h permeation study through rabbit skin mounted in Franz cell. The patches having no enhancer in the formulation also showed some drug release and permeation due to the presence of plasticizer. The results of the study suggested that new controlled release transdermal formulations of combined antiasthmatic drugs can be suitably developed as an alternate to conventional dosage forms.     

Bilayered transmucosal drug delivery system of pravastatin sodium: statistical optimization, in vitro, ex vivo, in vivo and stability assessment

The objective of the present study was to develop a mucoadhesive sustained release bilayered buccal patch of pravastatin sodium using Eudragit S100 as the base matrix so as to surmount hepatic first pass metabolism and gastric instability of the drug. A 32 full factorial design was employed to study the effect of independent variables viz. levels of HPMC K4M and carbopol 934P on % cumulative drug release, mucoadhesion time and mucoadhesive force. Amount of carbopol 934P and HPMC K4M significantly influenced characteristics like swelling index, in vitro mucoadhesive force, drug release, and mucoadhesion time. In vitro evaluation revealed that formulations exhibited satisfactory technological parameters. The mechanism of drug release was found to be non-Fickian diffusion. Different permeation enhancers were investigated to improve the permeation of drug from the optimized patches (F9) across the buccal mucosa. Formulation [F9 (P3)] containing 4% (v/v) dimethyl sulfoxide exhibited desirable permeation of drug. Histopathological studies performed using goat buccal mucosa revealed no mucosal damage. Bioavailability studies in rabbits demonstrated that [F9 (P3)] significantly higher C(max) (67.34?±?3.58?ng/ml) and AUC??∞ (350.27?±?9.59?ng/ml×h) (p < 0.05) of pravastatin sodium from optimized patch than IR tablet (C(max) 58.73?±?4.63?ng/ml and AUC??∞ 133.80?±?8.25?ng/ml×h). Formulation [F9 (P3)] showed sustained drug plasma concentration over a period of 10?h which was significantly longer than oral tablet (p < 0.05). Stability studies as per ICH guidelines established physical stability of the patch and chemical stability drug. The present study established potential of the optimized mucoadhesive buccal patches to circumvent the hepatic first-pass metabolism, gastric instability and to improve bioavailability of pravastatin sodium.     

Matrix-type transdermal drug delivery system of trandolapril: in vitro and ex vivo characterization

The purpose of the investigation was to develop and evaluate matrix-type transdermal drug delivery systems (TDDSs) of trandolapril. Matrix-type TDDSs of trandolapril were prepared by solvent evaporation technique. Eight formulations (composed of Eudragit RL 100 and Hydroxypropyl methyl cellulose 15 cps at a ratios of 2:8, 4:6, 6:4, 8:2 in formulations A1, A2, A3, A4; and Eudragit RS 100 and Hydroxypropyl methyl cellulose 15 cps in the same ratios in formulations B1, B2, B3, B4, respectively) were prepared. All formulations contained 5% w/w menthol as penetration enhancer and 15% w/w propylene glycol as plasticizer in ethanol as solvent. The prepared TDDSs were evaluated for physicochemical characteristics, in vitro release and ex vivo permeation. The physicochemical interactions between trandolapril and polymers were investigated by Fourier transform infrared spectroscopy. The results suggested that there is no physicochemical interaction between drug and polymers. The maximum drug release in 24 h for A series formulations was 95.45% (A1), 95.82% (A2), and it was 95.26% (B1), 95.69% (B2) for B series formulations, which are significantly (P < 0.05) different than the lowest values 78.79% (A3), 66.9% (A4) and 82.64% (B3), 71.67% (B4). The formulations A1 (flux 25.03 ± 0.98 μg/cm(2)/h) and B1 (flux 24.62 ± 0.63 μg/cm(2)/h) showed maximum skin permeation in the respective series. The flux obtained with formulations A1 and B1 meets the required flux (37.04 μg/h/cm(2)) with a minimum patch area (3.9 cm(2)). Matrix-type transdermal therapeutic systems of trandolapril could be prepared with the required flux using menthol as penetration enhancer.     

Mucoadhesive patches of Salbutamol sulphate for unidirectional buccal drug delivery: development and evaluation

Mucoadhesive buccal patches of Salbutamol Sulphate were prepared using five different polymers (polyvinylpyrrolidone [PVP]), polyvinyl alcohol [PVA], water soluble chitosan [CH(WS)], acid soluble chitosan [CH(AS)], hydroxypropyl methyl cellulose [HPMC])in various proportions and combinations (CH(WS)/PVP/HPMC, CH(WS)/PVA/HPMC, CH(AS)/PVP/HPMC, and CH(AS)/PVA/HPMC). A 3(2) full factorial design was used to design the experiments. A total of 72 patches were prepared. Thickness of the patches ranged between 0.3±0.003 and 0.6±0.009 mm. Mass of the patches were in the range of 68.12±4.6 to 95.02±7.2 mg. Patches showed increased mass whenever PEG -400 was used as plasticizer. The surface pH of patches were acidic to neutral (pH 4-pH 7). Patches showed satisfactory drug loading efficiency (85%to 97%). Eight formulations(C9, C18, C27, C36, D9, D18, D27, and D36)-which showed high folding endurance- were selected for further characterization. Patches with PEG -400 showed higher swelling index when compared to PG. The residence time of the patches ranged between 115 min and 120 min. Formulation C18 showed the maximum in vitro drug release of 101.4 % over a period of 120 min. Formulations D36 and C36 were best fitted to Higuchi model. The remaining formulations were best fitted to the Korsmeyer-Peppas model. Drug permeation was fast and showed the similar profile as that of the in vitro drug release. Patches were stable, during and at the end of the accelerated stability study.     

Development of domperidone bilayered matrix type transdermal patches: physicochemical, in vitro and ex vivo characterization

Background and the purpose of the study

Domperidone (DOM) is a dopamine- receptor (D₂) antagonist, which is widely used in the treatment of motion-sickness. The pharmacokinetic parameters make DOM a suitable candidate for transdermal delivery. The purpose of the present investigation was to develop transdermal delivery systems for DOM and to evaluate their physicochemical characteristics, in vitro release an ex vivo permeation through rat abdominal skin and their mechanical properties.

Methods

Bilayered matrix type transdermal drug delivery systems (TDDS) of DOM were prepared by film casting technique using hydroxypropyl methyl cellulose as primary and Eudragit RL 100 as secondary layers. Brij-35 was incorporated as a solubilizer, d-limonene and propylene glycol were employed as permeation enhancer and plasticizer respectively. The prepared TDDS were extensively evaluated for in vitro release, moisture absorption, moisture content, water vapor transmission, ex vivo permeation through rat abdominal skin, mechanical properties and stability studies. The physicochemical interaction between DOM and polymers were investigated by Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FTIR).

Results

All the formulations exhibited satisfactory physicochemical and mechanical characteristics. The optimized formulation F6 showed maximum cumulative percentage of drug release (90.7%), permeation (6806.64 µg) in 24 hrs, flux (86.02 µg /hr/cm²) and permeation coefficient of 0.86x10⁻² cm/hr. Values of tensile strength (4.34 kg/mm²) and elastic modulus (5.89 kg/cm²) revealed that formulation F6 was strong but not brittle. DSC and FTIR studies showed no evidence of interaction between the drug and polymers. A shelf life of 2 years is predicted for the TDDS.

Conclusions

Domperidone bilayered matrix type transdermal therapeutic systems could be prepared with the required flux and suitable mechanical properties.     

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.     

Intranasal mucoadhesive buspirone formulation: in vitro characterization and nasal clearance studies

Oral administration is unsuitable for drugs prone to extensive first-pass metabolism, like buspirone. Thus, in the present study an attempt has been made to develop a mucoadhesive intranasal formulation improving permeation characteristics of buspirone HCl. Nasal formulations containing different concentrations of chitosan HCl and hydroxypropyl-beta-cyclodextrins (HP-beta-CD) were prepared and compared with control buspirone HCl solution regarding permeability, in vitro duration of mucoadhesion, in vivo nasal clearance in rats and in vitro cytotoxicity on cell culture. Nearly two fold increase in buspirone permeation was observed with 1% chitosan HCl and a 3.5 fold increase with 1% chitosan HCI and 5% HP-beta-CD. Nasal clearance studies showed retention of 50% radioactivity up to about 3.5 h for formulation F7 containing 1% chitosan HCI compared to 1.5 h for control buspirone solution (F1). Results conclusively demonstrated enhancement in permeation with no cytotoxicity. Thus formulations can be used to improve bioavailability of buspirone HCl.