Preparation of highly porous gastroretentive metformin tablets using a sublimation method

The present investigation is aimed to formulate floating gastroretentive tablets containing metformin using a sublimation material. In this study, the release of the drug from a matrix tablet was highly dependent on the polymer concentrations. In all formulations, initial rapid drug release was observed, possibly due to the properties of the drug and polymer. The effect of the amount of PEO on swelling and eroding of the tablets was determined. The water-uptake and erosion behavior of the gastroretentive (GR) tablets were highly dependent on the amount of PEO. The water-uptake increased with increasing PEO concentration in the tablet matrix. The weight loss from tablets decreased with increasing amounts of PEO. Camphor was used as the sublimation material to prepare GR tablets that are low-density and easily floatable. Camphor was changed to pores in the tablet during the sublimation process. SEM revealed that the GR tablets have a highly porous morphology. Floating properties of tablets and tablet density were affected by the sublimation of camphor. Prepared floating gastroretentive tablets floated for over 24 h and had no floating lag time. However, as the amount of camphor in the tablet matrix increased, the crushing strength of the tablet decreased after sublimation. Release profiles of the drug from the GR tablets were not affected by tablet density or porosity. In pharmacokinetic studies, the mean plasma concentration of the GR tablets after oral administration was greater than the concentration of glucophase XR. Also, the mean AUC_0–∞ values for the GR tablets were significantly greater than the plasma concentrations of glucophase XR.     

Pharmacokinetics and analgesic effect of ketorolac floating delivery system

Abstract

Objectives: The efficacy of ketorolac tromethamine (KT) floating alginate beads as a drug delivery system for better control of KT release was investigated. The formulation with the highest drug loading, entrapment efficiency, swelling, buoyancy, and in vitro release would be selected for further in vivo analgesic effect in the mice and pharmacokinetics study in rats compared to the tablet dosage form.

Methods: KT floating alginate beads were prepared by extrusion congealing technique. KT in plasma samples was analyzed using a UPLC MS/MS assay.

Results: The percentage yield, drug loading and encapsulation efficiency were increased proportionally with the hydroxypropylmethyl cellulose (HPMC) polymer amount in the KT floating beads. A reverse relationship was observed between HPMC amount in the beads and the KT in vitro release rate. F3-floating beads were selected, due to its better in vitro results (continued floating for >8?h) than others. A longer analgesic effect was observed for F3 in fed mice as compared to the tablets. After F3 administration to rats, the C_max (2.2?±?0.3?µg/ml) was achieved at ～2?h and the decline in KT concentration was slower. F3 showed a significant increase in the AUC (1.89 fold) in rats as compared to the tablets.

Conclusion: KT was successfully formulated as floating beads with prolonged in vitro release extended to a better in vivo characteristic with higher bioavailability in rats. KT in floating beads shows a superior analgesic effect over tablets, especially in fed mice.     

In vitro and in vivo evaluation of ranitidine hydrochloride ethyl cellulose floating microparticles

The real issue in the development of oral controlled release dosage forms is not just to prolong the delivery of drugs but also to prolong the presence of dosage forms in the stomach in order to improve the bioavailability of drugs with a ‘narrow absorption window’. In the present study, an anti-ulcer drug, ranitidine hydrochloride, is delivered through a gastroretentive ethyl cellulose-based microparticulate system capable of floating on simulated gastric fluid for?>?12 h. Preparation of microparticles is done by solvent evaporation technique with modification by using an ethanol co-solvent system. The formulated microspheres were free flowing with good packability and encapsulation efficiencies were up to 96%. Scanning electron microscopy confirmed porous, spherical particles in the size range 300–750 µm. Microspheres showed excellent buoyancy and a biphasic controlled release pattern with 12 h. In vivo bioavailability studies performed on rabbits and T_max, C_max, AUC were calculated and confirmed significant improvement in bioavailability. The data obtained thus suggests that a microparticulate floating delivery system can be successfully designed to give controlled drug delivery, improved oral bioavailability and many other desirable characteristics.     

Phenylalanine-free taste-masked orodispersible tablets of fexofenadine hydrochloride: development,in vitro evaluation and in vivo estimation of the drug pharmacokinetics in healthy human volunteers

Abstract

Context: Fexofenadine hydrochloride (FXD) is a slightly soluble, bitter-tasting, drug having an oral bioavailability of 35%. The maximum plasma concentration is reached 2.6?h (T_max) post-dose.

Objective: Developing taste-masked FXD orodispersible tablets (ODTs) to increase extent of drug absorption and reduce T_max.

Methods: Taste masking was achieved via solid dispersion (SD) with chitosan (CS) or sodium alginate (ALG). Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffraction were performed to identify physicochemical interactions and FXD crystallinity. Taste-masked FXD-ODTs were developed via addition of superdisintegrants (croscarmellose sodium or sodium starch glycolate, 5% and 10%, w/w) or sublimable agents (camphor, menthol or thymol; 10% and 20%, w/w) to FXD-SDs. ODTs were evaluated for weight variation, drug-content, friability, wetting, disintegration and drug release. Camphor-based (20%, w/w) FXD-ODT (F12) was optimized (F23) by incorporation of a more hydrophilic lubricant (Pruv®), visualized via scanning electron microscopy and evaluated for FXD pharmacokinetics in healthy volunteers relative to Allegra® tablets.

Results: Based on gustatory sensation test, FXD–CS (1:1) and FXD–ALG (1:0.5) SDs were selected. Taste-masked FXD-ODTs had appropriate physicochemical properties. Drug release profiles of F23 and the phenylalanine-containing Allegra® ODT were similar (f₂?=?96). Pores were observed following camphor sublimation. The pharmacokinetic studies proved F23 ability to increase extent of FXD absorption and reduce T_max.     

Formulation,evaluation and pharmacokinetics of colon targeted pulsatile system of flurbiprofen

Objective: The intent of the present investigation is to develop colon targeted compression coated flurbiprofen pulsatile release tablets that retard the drug release in the upper gastro intestinal system but progressively release in the colon.

Materials and methods: Flurbiprofen core tablets were prepared by direct compression method and were compression coated with hydroxypropyl methylcellulose and Eudragit S100. The formulation is optimized based on the in vitro drug release study and further evaluated by X-ray imaging and pharmacokinetic studies in healthy humans for colonic delivery.

Results and discussions: The optimized formulation showed negligible drug release (7.26?±?0.05%) in the initial lag period followed by progressive release (99.27?±?0.46%) for 24?h. The X-ray imaging study in human volunteers showed that the tablets reached the colon without disintegrating in the upper gastrointestinal tract. The C_max of colon targeted tablets was 10792.62?ng/mL at T_max 10?h where as in case of immediate release tablets the C_max was 15684.79?ng/mL at T_max 3?h signifies the ability of compression coated tablets to target the colon.

Conclusion: Development of pulsatile release compression coated tablets using combination of time dependent and pH sensitive approaches was suitable to target the flurbiprofen to colon.     

Development of gastroretentive drug delivery system for cefuroxime axetil: In vitro and in vivo evaluation in human volunteers

The objective of this investigation was to develop the cefuroxime axetil sustained-release floating tablets to prolong the gastric residence time and compare their pharmacokinetic behavior with marketed conventional tablets (Zocef). The floating tablets were developed using polymers like HPMC K4M and HPMC K100M alone, and polymer combination of HPMC K4M and Polyox WSR 303 by effervescent technique. Tablets were prepared by slugging method and evaluated for their physical characteristics, in vitro drug release, and buoyancy lag time. The best formulation (F10) was selected based on in vitro characteristics and used in vivo radiographic and bioavailability studies in healthy human volunteers. All the formulations could sustain drug release for 12 h. The dissolution profiles were subjected to various kinetic release models and it was found that the mechanism of drug release followed Peppas model. The in vivo radiographic studies revealed that the tablets remained in stomach for 225±30 min. Based on in vivo performance, the developed floating tablets showed superior bioavailability than Zocef tablet. Based on in vivo performance significant difference was observed between C_max, t_max, t_1/2, AUC_0–∞, and mean residence time of test and reference (p<0.05). The increase in relative bioavailability of test was 1.61 fold when compared to reference.     

Influence of different types of low substituted hydroxypropyl cellulose on tableting,disintegration, and floating behaviour of floating drug delivery systems

The object of the present study is to evaluate the effect of application of low-substituted hydroxypropyl cellulose (L-HPC) 11 and B1 as excipients promoting floating in gastroretentive tablets. Directly compressed tablets were formed based on experimental design. Face-centred central composite design was applied with two factors and 3 levels, where amount of sodium alginate (X₁) and L-HPC (X₂) were the numerical factors. Applied types of L-HPCs and their 1:1 mixture were included in a categorical factor (X₃). Studied parameters were floating lag time, floating time, floating force, swelling behaviour of tablets and dissolution of paracetamol, which was used as a model active substance. Due to their physical character, L-HPCs had different water uptake and flowability. Lower flowability and lower water uptake was observed after 60 min at L-HPC 11 compared to L-HPC B1. Shorter floating times were detected at L-HPC 11 and L-HPC mixtures with 0.5% content of sodium alginate, whereas alginate was the only significant factor. Evaluating results of drug release and swelling studies on floating tablets revealed correlation, which can serve to help to understand the mechanism of action of L-HPCs in the field development of gastroretentive dosage forms.     

Formulation and evaluation of a gastroretentive dosage form of labetalol hydrochloride

Labetalol hydrochloride (LBT), 2-hydroxy-5-[1-hydroxy-2-[(1-methyl-3-phenylpropyl) amino] ethyl]-benzamide, a non-selective α, β-adrenoceptor antagonist is used in the treatment of hypertension. It shows variable bioavailability ranging from 10–80% which may be attributed to its minimum solubility in pH range 6 to 10, the pH conditions prevailing at the major site of absorption i.e. small intestine. Also due to its half life of 3 to 6 hrs it is administered twice daily. In the present work non-effervescent sustained release gastroretentive floating tablets of labetalol hydrochloride have been developed using various grades of HPMC and Poloxamer M127 as wetting agent. The tablets were evaluated for in vitro drug release, floating time, floating lag time, swelling studies etc. The tablets formulated with HPMC K4M CR and HPMC K15M CR along with Poloxamer showed negligible floating lag time with a total floating time over 12 hrs with complete release. Formulation was optimized using Stat-Ease Design Expert 7.1 software. Optimized batch was evaluated for the effect of change of osmolarity and pH on drug release, floating and swelling behaviour.     

盐酸维拉帕米脉冲控释片的研究

目的:制备适于临睡前服用、间隔4 h 后于次日凌晨释放出治疗药物的脉冲控释片。方法:以均匀设计优化盐酸维拉帕米压制包衣片的处方组成,体外溶出度测定、体内γ-闪烁扫描示踪考察药物释放滞后时间(T_lag) ,在家犬、人体内的药代动力学研究,考察脉冲控释片在体内控时效果。结果:均匀设计得出的多元线性回归方程优化筛选了控时3,4 ,5 h 的脉冲片处方,体外脉冲控时4 h 的IV 型脉冲片,在家犬体内和体外控时3 h 的III型脉冲片在受试者体内均实现给药后4 h 脉冲释放。结论:脉冲控释片仅改变了制剂的释药开始时间,而对药物的峰浓度、生物利用度等无影响,实现设计中的脉冲释放,为防治高血压的凌晨发作提供了良好的剂型选择。     

Formulation Design and Optimization of Orodispersible Tablets of Quetiapine Fumarate by Sublimation Method

The objective of present study was to formulate directly compressible orodispersible tablets of quetiapine fumarate by sublimation method with a view to enhance patient compliance. A full 3² factorial design was used to investigate the effect of two variables viz., concentration of Indion 414 and camphor. Indion 414 (3-5 % w/w) was used as superdisintegrant and camphor (5-15 % w/w) as subliming agent. The tablets were evaluated for thickness, weight variation, hardness, friability, content uniformity, wetting time, porosity, in vitro disintegration time and in vitro drug release. The formulation containing 5% w/w of Indion 414 and 5% w/w camphor was emerged as promising based on evaluation parameters. The disintegration time for optimized formulation was 18.66 s. The tablet surface was evaluated for presence of pores by scanning electron microscopy before and after sublimation. Differential scanning colorimetric study did not indicate any drug excipient incompatibility, either during mixing or after compression. The effect of independent variables on disintegration time, % drug release and friability is presented graphically by surface response plots. Short-term stability studies on the optimized formulation indicated no significant changes in drug content and in vitro disintegration time. The directly compressible orodispersible tablets of quetiapine fumarate with lower friability, greater drug release and shorter disintegration times were obtained using Indion 414 and camphor at optimum concentrations.     

Calendar

The objective of the present study was to develop a colon targeted system of meloxicam for potential application in the prophylaxis of colorectal cancer. Efficacy of selective cyclooxygenase–2 inhibitors has been proven in colorectal cancer. Meloxicam is a selective cyclooxygenase–2 inhibitor with pH-dependent solubility. To achieve pH-independent drug release of meloxicam, pH modifying agents (buffering agents) were used. Meloxicam tablets containing polyethylene oxide were dually coated with ethyl cellulose containing hydrophilic material, polyethylene glycol as an inner coating layer and methyl acrylate, methyl methacrylate, and methacrylic acid copolymer (Eudragit^® FS 30D) as outer coating layer for colon targeting. Optimized tablet formulations demonstrated good potential to deliver the drug to the colon by successfully exhibiting a lag time of 5?h during in vitro drug release study. An in vivo evaluation study conducted to ascertain pharmacokinetic parameters in rabbits revealed that the onset of drug absorption from the coated tablets (T_{lag time}?=?4.67?±?0.58?h) was significantly delayed compared to that from the uncoated tablets. The AUC_0→t and AUC_0→∞ for coated tablets were lower than of uncoated tablets, although the difference was not significant (p?>?0.01). The roentgenography study revealed that the tablet remained intact, until it reached the colon (5?h), which demonstrates that the system can efficiently deliver the drug to the colon. This study demonstrated that a meloxicam-loaded colon targeted system exhibited promising targeting and hence may be used for prophylaxis of colorectal cancer.     

Intra- and Inter-Subject Variabilities of CGP 33101 after Replicate Single Oral Doses of Two 200-mg Tablets and 400-mg Suspension

Purpose. The purpose of this study was to use a replicate designed trial to assess the overall, intra- and inter-subject variabilities in pharmacokinetic parameters of CGP 33101 after oral administration of tablets relative to that of powder suspended in water, and to determine the relative proportion of the intra-subject variance to the overall variability. Methods. Sixteen healthy subjects were randomly assigned to four groups to receive tablets and suspension twice in four different treatment sequences. The plasma concentration-time profile of CGP 33101 was characterized in terms of C_max, T_max, and AUC. Bioavailability of tablets relative to suspension and intra- and inter-subject variability were assessed by statistical analysis. Results and Conclusions. The overall variabilities in absorption kinetics of CGP 33101 in healthy subjects were small with CV's of the population mean values for AUC and C_max less than 26% for both tablets and suspension. Contribution of intra-subject variability to the overall variability was also small (~20%). Both the overall and intra-subject variabilities of AUC and C_max after suspension were larger than after the tablets. However, the differences in variability between tablets and suspension were not statistically significant (p > 0.05). The tablet formulation was bioequivalent to suspension in terms of rate and extent of absorption based on 90% conventional confidence intervals (for AUC and C_max) and Wilcoxon rank-sum test (for T_max).     

Bumadizone calcium dihydrate microspheres compressed tablets for colon targeting: formulation,optimization and in vivo evaluation in rabbits

Abstract

The objective of this study was the development of a colon-targeted microspheres which were compressed into tablets containing the non-steroidal anti-inflammatory bumadizone calcium dihydrate. A 3² full factorial design was adopted for the evaluation of the prepared microspheres. The effect of two independent variables namely polymer type (Eudragit RS100, ethyl cellulose and cellulose acetate butyrate), and drug: polymer ratio (1:1, 9:1 and 18:1) was studied on the entrapment efficiency and in vitro drug release for 12?h. Colon targeting aims to minimize the release of the drug off target area (pH 1.2 and 6.8) and to maximize the release of the drug in target area (pH 7.4). Candidate formulae were compressed into core tablets and colon targeting was achieved using the enzyme-dependent polymer (pectin) as coat in three different concentrations 50, 75 and 90%. Candidate formula F15 (microspheres prepared using BDZ:CAB in a ratio of 18:1 and compressed into tablets using 50% pectin and 50% Avicel in the coat) was able to adequately modulate drug release avoiding drug release in the gastric ambient, and reaching the colonic targeting where 99.7% release was achieved within 12?h following zero-order model. In vivo studies showed that F15 achieved significant decrease in myeloperoxidase activity and inflammation with delayed T_max (4?h) and lower C_max (2700?ng/ml) when compared to marketed product.     

Formulation and evaluation of famotidine floating tablets

The purpose of this investigation was to prepare a gastroretentive drug delivery system of famotidine. Floating tablets of famotidine were prepared employing two different grades of methocel K100 and methocel K15M by effervescent technique; these grades of methocel were evaluated for their gel forming properties. Sodium bicarbonate was incorporated as a gas-generating agent. The floating tablets were evaluated for uniformity of weight, hardness, friability, drug content, in vitro buoyancy and dissolution studies. The effect of citric acid on drug release profile and floating properties was investigated. The prepared tablets exhibited satisfactory physico-chemical characteristics. All the prepared batches showed good in vitro buoyancy. The tablet swelled radially and axially during in vitro buoyancy studies. It was observed that the tablet remained buoyant for 6-10 hours. Decrease in the citric acid level increased the floating lag time but tablets floated for longer duration. A combination of sodium bicarbonate (130mg) and citric acid (10mg) was found to achieve optimum in vitro buoyancy. The tablets with methocel K100 were found to float for longer duration as compared with formulations containing methocel K15M. The drug release from the tablets was sufficiently sustained and non-Fickian transport of the drug from tablets was confirmed.     

Delayed-release tablets using hydroxyethylcellulose as a gel-forming matrix

Delayed-release tablets containing diltiazem hydrochloride (DIL) were prepared by using CM-type hydroxyethylcellulose (HEC) of three viscosity grades. The tablets consisted of a core containing 30 mg of DIL and an outer shell formed by compressing HEC. DIL in the core was rapidly released from the tablets after a lag time of several hours in all cases. The lag time to the start of release of DIL was more prolonged with an increase in viscosity of CM-type HEC. The rate of water-uptake was greater in the CM-L4 type HEC tablet of a low viscosity grade (14 cps) than those in CM-L3 and CM-L2 type HEC (27 and 95 cps, respectively) tablets. There was little difference in lag time to the start of release of DIL from CM-type HEC tablets between JP XII 1st (pH 1.2) and 2nd (pH 6.8) fluids. A human volunteer study was performed using the delayed-release tablets prepared with CM-type HEC of two or three viscosity grades. The t_maxand MRT values of CM-type HEC tablets were significantly increased with an increase in viscosity of HEC and showed only small variations between subjects, respectively. On the other hand, although the AUC values were almost the same, the C_max values decreased with prolongation of lag time. The lag time in vivo for appearance of DIL in the blood corresponded well to the lag time in vitro for drug release, but tended to be shortened as compared with the lag time in vitro. These results indicate that the lag time can be optionally controlled by selecting HEC with a proper viscosity and/or by changing the amount of HEC forming the outer shell. This delayed-release tablet using HEC will be useful for control of time-related symptoms which need time-controlled or site-specific delivery in the gastrointestinal tract.     

Stability and bioavailability of diltiazem/polyethylene oxide matrix tablets

Abstract

The aim of this study was to prepare and evaluate in vitro and in vivo; Diltiazem-Hydrochloride (DTZ) in sustained-release matrix tablets. Stability of DTZ tablets prepared with polyethylene oxide (MWs 900?000, 4?000?000, and 8?000?000) with or without addition of electrolytes was carried-out for 1-month, under short-term storage at 40?°C/75% RH. Stability was evaluated by DTZ content, DSC and drug release using the Flow-Through Cell (USP # IV). The majority of stored tablets were stable for 1-month under short-term storage with respect to DTZ content and drug release. DSC curves of stored samples showed appearance of new exothermic peak after 1-month storage at 40?°C/75% RH, which was not observed after 5?years storage at room temperature. A selected formula was tested in vivo against reference product on eight healthy human volunteers. DTZ-plasma profiles were different between the two formulae. However, no statistically significant differences were detected between C_max, AUC_0–48 and AUC_0–∞. The two products were therapeutically in-equivalent, as 90% confidence intervals “T/R” were 88.82–205.76, 91.40–139.94, and 93.73–134.97 for C_max, AUC_0–48 and AUC_0–∞, respectively. This study highlighted possible differences observed between the two regimes frequently applied for stability testing.     

Pharmacokinetic profile of a new form of sumatriptan tablets in healthy volunteers

SUMMARY

Objective: Rapid delivery of migraine-specific medication to its site(s) of action is thought to be crucial in preventing or minimizing sensitization of central pain pathways and thereby in optimizing pain-free outcomes in patients with migraine. Sumatriptan has been developed as a new tablet formulation to enhance the rate of systemic drug delivery by improving tablet disintegration and drug dispersion relative to those of conventional tablets. These enhanced formulation characteristics may be beneficial during occurrences of the gastric stasis that can accompany migraine.

Methods: This randomized, open-label, 4-way crossover study (n = 32) was conducted to determine whether the new formulation of sumatriptan 50 and 100?mg is bioequivalent to sumatriptan conventional tablets and to compare the pharmacokinetic profiles of the new formulation and the conventional tablet during the early (0–2?h) post-dose interval in healthy volunteers. Pharmacokinetics during the early post-dose interval are important in determining a drug's onset of action, an important parameter to patients with migraine.

Results: The results confirm that the new formulation of sumatriptan and sumatriptan conventional tablets are bioequivalent as demonstrated by the finding that the 90% confidence intervals for the sumatriptan area under the concentration time curve to infinity and to the last evaluable time point (AUC_0–∞ and AUC_0–t, respectively) and maximum plasma concentration (C_max) fell within the predetermined bounds defining bioequivalence (0.80–1.25) for both doses. Pharmacokinetic parameters measured early (0–2?h) after dosing reveal slightly faster absorption, on average, of the new sumatriptan formulation than sumatriptan conventional tablets although high intersubject variability was observed. For the new sumatriptan formulation, AUC_0–2 (AUC up to 2h post-dose) was, on average, 1% greater (50?mg) and 8% greater (100?mg) and maximal sumatriptan levels were attained, on average, 10?min earlier (50?mg) and 15?min earlier (100?mg) compared with the conventional tablet. Other measures including AUC_0–0.5 (AUC to 30?min post-dose), times to achieve sumatriptan concentrations of 5 and 10?ng/mL, and mean percentage C_max 15, 20 and 30?min post-dose demonstrate an observable improvement in rate of drug absorption for the new form of sumatriptan compared with conventional tablets.

Conclusion: The new form of sumatriptan is bioequivalent to sumatriptan conventional tablets and is absorbed more quickly than conventional tablets.     

Mucoadhesive bilayer buccal tablet of carvedilol-loaded chitosan microspheres: in vitro,pharmacokinetic and pharmacodynamic investigations

A multiple-unit system comprising mucoadhesive bilayer buccal tablets of carvedilol-loaded chitosan microspheres (CMs) was developed to improve bioavailability and therapeutic efficacy of carvedilol. Drug-loaded CMs were prepared by spray drying, evaluated for powder and particle characteristics, and optimized batch of CMs was compressed into bilayer buccal tablets using Carbopol. Tablets were evaluated for physicochemical parameters, in vitro drug release, in vivo pharmacokinetic and pharmacodynamic studies. Optimized formulation, CMT1 (CMT, chitosan microsphere tablet) showed maximum mucoadhesive force (50?±?1.84?dyne/cm²), exhibited 73.08?±?3.05% drug release and demonstrated zero-order kinetics with non-Fickian release mechanism. Pharmacokinetic studies in rabbits showed significantly higher C_max (71.26?±?6.45?ng/mL), AUC_0–10 (AUC, area under the curve 390.75?±?5.23?ng/mL/h) and AUC_0–∞ (664.72?ng/mL/h) than carvedilol oral tablet. Pharmacodynamic studies confirmed reduction in mean arterial pressure, heart rate, body weight and triglyceride on administration of bilayer buccal tablet compared to oral carvedilol tablet. Multiple-unit system exhibited enhanced bioavailability and sustained release of carvedilol, indicating its improved therapeutic potential for the treatment of hypertension.     

Design,Development and Optimization of S (-) Atenolol Floating Sustained Release Matrix Tablets Using Surface Response Methodology

The objective of this present investigation was to develop and formulate floating sustained release matrix tablets of s (-) atenolol, by using different polymer combinations and filler, to optimize by using surface response methodology for different drug release variables and to evaluate the drug release pattern of the optimized product. Floating sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: Hydroxypropyl methylcellulose, sodium bicarbonate as a gas generating agent, polyvinyl pyrrolidone as a binder and lactose monohydrate as filler. The 3² full factorial design was employed to investigate the effect of formulation variables on different properties of tablets applicable to floating lag time, buoyancy time, % drug release in 1 and 6 h (D_{1 h,}D_{6 h}) and time required to 90% drug release (t_90%). Significance of result was analyzed using analysis of non variance and P < 0.05 was considered statistically significant. S (-) atenolol floating sustained release matrix tablets followed the Higuchi drug release kinetics that indicates the release of drug follows anomalous (non-Fickian) diffusion mechanism. The developed floating sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet.     

甲硝唑胃部滞留制剂的制备

目的为更好地清除幽门螺旋杆菌,制备同时具有缓释、漂浮、黏附特性的甲硝唑胃部滞留制剂。方法采用挤出滚圆法制备丸心,流化床包衣法制备甲硝唑缓释漂浮黏附微丸。EudragitNE30D为缓释层,NaHCO3为产气层,EudragitRL 30D为阻滞层,Carbopol 934P为黏附层,考察不同包衣增量情况下,各微丸的释药行为,在0.1 mol.L-1HCl中的漂浮性能,及离体大鼠胃黏膜上的黏附能力。结果丸心外包质量分数为3%的EudragitNE 30D,质量分数为9%的NaHCO3,质量分数为10%的EudragitRL 30D,质量分数为5%的Carbopol 934P的微丸,能实现缓释12 h、4 min起漂、持续漂浮12 h,漂浮率大于95%、黏附率为100%。结论所制备的甲硝唑胃部滞留制剂,同时具备缓释的释药行为、优良的漂浮能力、良好的黏附特征。进而能增加甲硝唑的胃部滞留时间,延长药物与幽门螺旋杆菌的接触时间,提高甲硝唑抗幽门螺旋杆菌的疗效。