盐酸倍他司汀片联合盐酸氟桂利嗪片对椎-基底动脉供血不足性眩晕症患者椎基底动脉血流动力学和生活质量的影响

摘要 目的：观察盐酸倍他司汀片联合盐酸氟桂利嗪片对椎-基底动脉供血不足（VBI）性眩晕症患者椎基底动脉血流动力学和生活质量的影响。方法：选择2019年5月~2021年2月期间来我院就诊的97例VBI性眩晕症患者,根据乱数表法,入选的患者分为对照组和观察组,分别为48例和49例,对照组接受盐酸倍他司汀片治疗,观察组接受盐酸倍他司汀片联合盐酸氟桂利嗪片治疗,均治疗2周。对比两组疗效、药物不良反应、眩晕症状评分、生活质量、椎基底动脉血流动力学情况。结果：观察组的临床总有效率（93.88%）高于对照组（72.92%）（P<0.05）。治疗2周后,观察组的眩晕评定量表的评分系统（DARS）、眩晕障碍量表（DHI）评分低于对照组（P<0.05）。治疗2周后,观察组的36项健康调查简表（SF-36）各维度评分均高于对照组（P<0.05）。治疗2周后,观察组的左侧/右侧椎动脉及基底动脉血流速度较对照组高（P<0.05）。两组不良反应发生率对比无差异（P>0.05）。结论：盐酸倍他司汀片联合盐酸氟桂利嗪片治疗VBI性眩晕症患者疗效显著,可有效改善其椎基底动脉血流动力学状况,缓解眩晕症状,提高生活质量。     

Fabrication of Triple-Layer Matrix Tablets of Venlafaxine Hydrochloride Using Xanthan Gum

The objective of present investigation was to develop venlafaxine hydrochloride-layered tablets for obtaining sustained drug release. The tablets containing venlafaxine hydrochloride 150 mg were prepared by wet granulation technique using xanthan gum in the middle layer and barrier layers. The granules and tablets were characterized. The in vitro drug dissolution study was conducted in distilled water. The tablets containing two lower strengths were also developed using the same percentage composition of the middle layer. Kinetics of drug release was studied. The optimized batches were tested for water uptake study. Radar diagrams are provided to compare the performance of formulated tablets with the reference products, Effexor XR capsules. The granules ready for compression exhibited good flow and compressibility when xanthan gum was used in the intragranular and extragranular fractions. Monolayer tablets failed to give the release pattern similar to that of the reference product. The drug release was best explained by Weibull model. A unified Weibull equation was evolved to express drug release from the formulated tablets. Lactose facilitated drug release from barrier layers. Substantial water uptake and gelling of xanthan gum appears to be responsible for sustained drug release. The present study underlines the importance of formulation factors in achieving same drug release pattern from three strengths of venlafaxine hydrochloride tablets.     

Fabrication of Modified Release Tablet Formulation of Metoprolol Succinate using Hydroxypropyl Methylcellulose and Xanthan Gum

The present investigation was undertaken to fabricate modified release tablet of metoprolol succinate using hydroxypropyl methylcellulose (HPMC) and xanthan gum as a matrixing agent. A 3² full factorial design was employed for the optimization of formulation. The percentage drug released at a given time (Y ₆₀, Y ₂₄₀ and Y ₇₂₀) and the time required for a given percentage of drug to be released (t _50%) were selected as dependent variables. The in vitro drug dissolution study was carried out in pH 6.8 phosphate buffer employing paddle rotated at 50 rpm. The similarity factor (f ₂) was calculated for selection of best batch considering mean in vitro dissolution data of Seloken® XL as a reference profile. It is concluded that the desired drug release pattern can be obtained by using a proper combination of HPMC (high gelling ability) and xanthan gum (quick gelling tendency). The economy of xanthan gum and faster hydration rate favors its use in modified release tablets. The matrix integrity during dissolution testing was maintained by using hydroxypropyl methylcellulose.     

Formulation and Evaluation of Bioadhesive Buccal Drug Delivery of Tizanidine Hydrochloride Tablets

The study aim was concerned with formulation and evaluation of bioadhesive buccal drug delivery of tizanidine hydrochloride tablets, which is extensively metabolized by liver. The tablets were prepared by direct compression using bioadhesive polymers such as hydroxylpropyl methylcellulose K4M, sodium carboxymethyl cellulose alone, and a combination of these two polymers. In order to improve the permeation of drug, different permeation enhancers like beta-cyclodextrin (β-CD), hydroxylpropyl beta-cyclodextrin (HP-β-CD), and sodium deoxycholate (SDC) were added to the formulations. The β-CD and HP-β-CD were taken in 1:1 molar ratio to drug in formulations. Bioadhesion strength, ex vivo residence time, swelling, and in vitro dissolution studies and ex vivo permeation studies were performed. In vitro release of optimized bioadhesive buccal tablet was found to be non-Fickian. SDC was taken in 1%, 2%, and 3% w/w of the total tablet weight. Stability studies in natural saliva indicated that optimized formulation has good stability in human saliva. In vivo mucoadhesive behavior of optimized formulation was performed in five healthy male human volunteers and subjective parameters were evaluated.     

Impact of Chiral Bioanalytical Methods on the Bioequivalence of Ibuprofen Products Containing Ibuprofen Lysinate and Ibuprofen Base

The purpose was to assess the impact of the use of a chiral bioanalytical method on the conclusions of a bioequivalence study that compared two ibuprofen suspensions with different rates of absorption. A comparison of the conclusion of bioequivalence between a chiral method and an achiral approach was made. Plasma concentrations of R‐ibuprofen and S‐ibuprofen were determined using a chiral bioanalytical method; bioequivalence was tested for R‐ibuprofen and for S‐ibuprofen separately and for the sum of both enantiomers as an approach for an achiral bioanalytical method. The 90% confidence interval (90% CI) that would have been obtained with an achiral bioanalytical method (90% CI: C_max: 117.69–134.46; AUC₀^t: 104.75–114.45) would have precluded the conclusion of bioequivalence. This conclusion cannot be generalized to the active enantiomer (90% CI: C_max: 103.36–118.38; AUC₀^t: 96.52–103.12), for which bioequivalence can be concluded, and/or the distomer (90% CI: C_max: 132.97–151.33; AUC₀^t: 115.91–135.77) for which a larger difference was observed. Chiral bioanalytical methods should be required when 1) the enantiomers exhibit different pharmacodynamics and 2) the exposure (AUC or C_max) ratio of enantiomers is modified by a difference in the rate of absorption. Furthermore, the bioequivalence conclusion should be based on all enantiomers, since the distomer(s) might not be completely inert, in contrast to what is required in the current regulatory guidelines. In those cases where it is unknown if the ratio between enantiomers is modified by changing the rate of absorption, chiral bioanalytical methods should be employed unless enantiomers exhibit the same pharmacodynamics. Chirality 28:429–433, 2016. © 2016 Wiley Periodicals, Inc.     

Formulation, evaluation, and comparison of bilayered and multilayered mucoadhesive buccal devices of propranolol hydrochloride

The purpose of this research work was to establish mucoadhesive buccal devices of propranolol hydrochloride (PRH) in the forms of bilayered and multilayered tablets. The tablets were prepared using sodium carboxymethylcellulose (SCMC) and Carbopol-934 (CP) as bioadhesive polymers to impart mucoadhesion and ethyl cellulose (EC) to act as an impermeable backing layer. Buccal devices were evaluated by different parameters such as weight uniformity, content uniformity, thickness, hardness, surface pH, swelling index, ex vivo mucoadhesive strength, ex vivo mucoadhesion time, in vitro drug release, and in vitro drug permeation. As compared with bilayered tablets, multilayered tablets showed slow release rate of drug with improved ex vivo bioadhesive strength and enhanced ex vivo mucoadhesion time. The mechanism of drug release was found to be non-Fickian diffusion (value of n between 0.5 and 1.0) for both the buccal devices. The stability of drug in both the optimized buccal devices was tested for 6 hours in natural human saliva; both the buccal devices were found to be stable in natural human saliva. The present study concludes that mucoadhesive buccal devices of PRH can be a good way to bypass the extensive hepatic first-pass metabolism and to improve the bioavailability of PRH. Published: March 16, 2007     

Anhydride Prodrug of Ibuprofen and Acrylic Polymers

The objective of this study was to synthesize anhydride prodrugs for carboxylic-acid-bearing agents such as non-steroidal anti-inflammatory drugs, shield the carboxylic acid group from irritative effects, and obtain sustained release patterns. Ibuprofen was used as a representative drug for anhydride derivatization. Conjugates of ibuprofen with carboxylic acid moieties of different acrylic polymers were prepared by dehydration reaction using acetic anhydride. Products were characterized by infrared spectroscopy, nuclear magnetic resonance, and scanning electron microscopy followed by preparation of microspheres with different sizes from the conjugate Eudragit® L-100-ibuprofen. The drug release was monitored by high-performance liquid chromatography. Ibuprofen was bound to the polymers via an anhydride bond in high reaction yields (75–95%) with drug loading of up to 30% (w/w). These anhydride derivatives hydrolyzed and release the drug at different periods ranging from 1 to 5 days, depending on the hydrophobicity and the cross-linking of the conjugates. The release of drug from the microspheres was correlated to their size and ranged from 2 to almost 8 days. This study demonstrates the promise of anhydride prodrug for extending drug action while shielding the carboxylic acid group.     

Formulation and Evaluation of Swellable and Floating Gastroretentive Ciprofloxacin Hydrochloride Tablets

Drugs that have narrow absorption window in the gastrointestinal tract (GIT) will have poor absorption. For these drugs, gastroretentive drug delivery systems offer the advantage in prolonging the gastric emptying time. Swellable, floating, and sustained release tablets are developed by using a combination of hydrophilic polymer (hydroxypropyl methylcellulose), swelling agents (crospovidone, sodium starch glycolate, and croscarmelose sodium) and effervescent substance (sodium bicarbonate). Formulations are evaluated for percentage swelling, in vitro drug release, floating lag time, total duration of floating, and mean residence time (MRT) in the stomach. The drug release of optimized formulation follows the Higuchi kinetic model, and the mechanism is found to be non-Fickian/anomalous according to Krosmeyer–Peppas (n value is 0.68). The similarity factor (f ₂) is found to be 26.17 for the optimized formulation, which the release is not similar to that of marketed produced (CIFRAN OD®). In vivo nature of the tablet at different time intervals is observed in the radiographic pictures of the healthy volunteers and MRT in the stomach is found to be 320?±?48.99 min (n?=?6). A combination of HPMC K100M, crospovidone, and sodium carbonate shows the good swelling, drug release, and floating characters than the CIFRAN OD®.     

Formulation and Evaluation of Gastroretentive Drug Delivery System of Propranolol Hydrochloride

The objective of present study was to develop a gastroretentive drug delivery system of propranolol hydrochloride. The biggest problem in oral drug delivery is low and erratic drug bioavailability. The ability of various polymers to retain the drug when used in different concentrations was investigated. Hydroxypropyl methylcellulose (HPMC) K4 M, HPMC E 15 LV, hydroxypropyl cellulose (HPC; Klucel HF), xanthan gum, and sodium alginate (Keltose) were evaluated for their gel-forming abilities. One of the disadvantages in using propranolol is extensive first pass metabolism of drug and only 25% reaches systemic circulation. The bioavailability of propranolol increases in presence of food. Also, the absorption of various drugs such as propranolol through P-glycoprotein (P-gp) efflux transporter is low and erratic. The density of P-gp increases toward the distal part of the gastrointestinal tract (GIT). Therefore, it was decided to formulate floating tablet of propranolol so that it remains in the upper part of GIT for longer time. They were evaluated for physical properties, in vitro release as well as in vivo behavior. In preliminary trials, tablets formulated with HPC, sodium alginate, and HPMC E 15 LV failed to produce matrix of required strength, whereas formulation containing xanthan gum showed good drug retaining abilities but floating abilities were found to be poor. Finally, floating tablets were formulated with HPMC K4 M and HPC.     

Bioadhesive Microspheres for Bioavailability Enhancement of Raloxifene Hydrochloride: Formulation and Pharmacokinetic Evaluation

Raloxifene hydrochloride (R-HCl), a BCS class II drug, remains a mainstay in the prevention and pharmacologic therapy of osteoporosis. Its absolute bioavailability, however, is 2% due to poor solubility and extensive first pass metabolism. The present study describes two simultaneous approaches to improve its bioavailability, complexation of R-HCl with cyclodextrin(s), and formulation of mucoadhesive microspheres of the complex using different proportions of carbopol and HPMC. Microspheres were pale yellow in color, free-flowing, spherical, and porous in outline. The particle size ranged between 3 and 15 μm, and entrapment efficiency was found to be within 81.63% to 87.73%. A significant improvement in the solubility of R-HCl was observed, and it differed with the combination of excipients used. X-ray diffraction and differential scanning calorimetry studies revealed that enhancement in drug solubility was resulted due to a change in its crystallinity within the formulation. Microspheres possessed remarkable mucoadhesion and offered controlled drug release, lasting up to 24 h. They produced a sharp plasma concentration–time profile of R-HCl within 30 min post-administration to Wistar rats. [AUC]_0–24 h was found to be 1,722.34 ng h/ml, and it differed significantly to that of pure drug powder (318.28 ng h/ml). More than fivefold increase in AUC and more than twofold increase in MRT were observed. FT-IR studies evidenced no interaction among drug and excipients. The results of this study showed that mucoadhesive microspheres could be a viable approach to improve the pharmacokinetic profile of R-HCl.     

Taste Mask, Design and Evaluation of an Oral Formulation Using Ion Exchange Resin as Drug Carrier

The purpose of this research was to mask the bitter taste of Diphenhydramine Hydrochloride (DPH) using cation exchange resins. Indion 234 and Tulsion 343 that contained crosslinked polyacrylic backbone were used. The drug resin complexes (DRC) were prepared by batch process by taking drug: resin ratios 1:1, 1:2, and 1:3. The optimum drug: resin ratio and the time required for maximum complexation was determined. The drug resinates were evaluated for the drug content, taste, micromeritic properties drug release and X-ray diffraction (PXRD). Effervescent and dispersible tablets were developed from optimum drug: resin ratios of 1:2 and 1:1. The formulations were evaluated for uniformity of dispersion, disintegration time, and in vitro dissolution. The X-ray diffraction study confirmed the monomolecularity of entrapped drug in the resin beads. The taste evaluation depicted the successful taste masking of DPH with drug resin complexes. The drug release of 95% in 15 min was observed for effervescent and dispersible tablets.     

Optimization Studies on Design and Evaluation of Orodispersible Pediatric Formulation of Indomethacin

In the present study, the aim was to optimize an orodispersible formulation of indomethacin using a combined approach of subliming agent and superdisintegrant. The tablets were made by non-aqueous wet granulation technique with superdisintegrant incorporated both intragranularly and extragranularly. A 2³ factorial design was used to investigate the effects amount of subliming agents namely camphor and ammonium bicarbonate and taste masking and soothening hydrophilic agent mannitol as independent variables and disintegration time and crushing strength as dependent responses. The volatilization time of eight hours at 50°C was optimized by conducting solid-state kinetic studies of optimized formulations. Optimized orodispersible tablets were evaluated for wetting time, water absorption ratio, porosity and in vitro and in vivo disintegration tests. Results show that higher levels of camphor and mannitol and a lower level of ammonium bicarbonate is desirable for orodispersion. Scanning electron microscopy (SEM) revealed the porous surface morphology and kinetic digital images substantiated the orodispersible property. Differential Scanning Calorimetry (DSC) studies exhibited physiochemical compatibility between indomethacin and various excipients used in the tablet formulation. Stability studies carried out as per ICH Q₁ A guidelines suggested the stable formulations for the tested time period of 6 months. The systematic approach of using subliming and disintegrating agents helped in achieving a stable, optimized orodispersible formulation, which could be industrially viable.     

Formulation and In Vitro,In Vivo Evaluation of Effervescent Floating Sustained-Release Imatinib Mesylate Tablet

Introduction

Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT). Conventional imatinib mesylate (Gleevec) tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets.

Methodology

Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M), with Sodium alginate (SA) and Carbomer 934P (CP) as release-retarding polymers, sodium bicarbonate (NaHCO₃) as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec) in 0.1 N HCl (pH 1.2) at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted.

Results and Discussion

Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO₃ produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower C_max and higher T_max compared to the conventional tablet (Gleevec). Thus, formulated SR tablets preserved persistent concentration of plasma up to 24 hours.

Conclusion

In conclusion, in order to suggest a better drug delivery system with constant favorable release, resulting in optimized absorption and less side effects, formulated CP-HPMC-SA based imatinib mesylate floating sustained-release tablets can be a promising candidate for cancer chemotherapy.     

Polymeric Matrix System for Prolonged Delivery of Tramadol Hydrochloride, Part I: Physicochemical Evaluation

Management of moderate or severe chronic pain conditions is the burden of clinicians dealing with patients trying to improve their quality of life and diminish their suffering. Although not a new opioid, tramadol has been recently rediscovered and widely used; this may be due to its favorable chronic safety and dependence profiles together with its high potency. Tramadol is a centrally acting analgesic with half-life of ~6 h; therefore, it requires frequent dosing. It is freely soluble in water; hence, judicious selection of retarding formulations is necessary. The current study is focused on the innovation of a novel, simple, monolayer, easy-to-use, cost-effective, and aesthetically acceptable bioadhesive transdermal delivery system overcoming the defects of the conventional “patch” as carrier system for tramadol, ensuring its adequate delivery, along with the physicochemical evaluation of the designed formulations. Monolithic tramadol matrix films of chitosan, different types of Eudragit®, and binary mixtures of both were prepared. As a single-polymer film, chitosan film showed best properties except for somewhat high moisture uptake capacity, insufficient strength and rapid release, and permeation. Polymer blends were monitored in order to optimize both properties and performance. Promising results were obtained, with chitosan–Eudragit® NE30D (1:1) film showing the most desirable combined, sufficiently rapid as well as prolonged release and permeation profiles along with satisfactory organoleptic and physicochemical properties.     

胃复春片联合兰索拉唑肠溶片对慢性萎缩性胃炎患者血清胃肠激素、炎症因子及免疫功能的影响

摘要 目的：胃复春片联合兰索拉唑肠溶片对慢性萎缩性胃炎（CAG）患者血清胃肠激素、炎症因子及免疫功能的影响。方法：选取62例CAG患者,根据门诊挂号奇偶性分为对照组（n=31,兰索拉唑肠溶片治疗）和研究组（n=31,胃复春片联合兰索拉唑肠溶片治疗）。比较两组患者疗效、胃肠激素[胃泌素(GAS)、胃动素(MTL)]、炎症因子[超敏C反应蛋白（hs-CRP）、肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）]、免疫功能及不良反应。结果：研究组治疗2个月后的总有效率为87.10%（27/31）,高于对照组的64.52%（20/31）,差异有统计学意义（P<0.05）。治疗2个月后,研究组hs-CRP、TNF-α、IL-6、GAS、CD8P低于对照组,MTL、CD4P、CD4⁺/CD8⁺高于对照组（P<0.05）。两组不良反应发生率对比未见明显差异（P>0.05）。结论：胃复春片联合兰索拉唑肠溶片治疗CAG疗效确切,可有效改善机体胃肠激素、炎症因子水平及免疫功能,且安全可靠,具有一定应用价值。     

Thermoreversible Nasal In situ Gel of Venlafaxine Hydrochloride: Formulation, Characterization, and Pharmacodynamic Evaluation

In order to improve the bioavailability of the antidepressant drug, venlafaxine hydrochloride, in situ mucoadhesive thermoreversible gel, was formulated using Lutrol F127 (18%) as a thermo gelling polymer. Mucoadhesion was modulated by trying carbopol 934, PVP K30, HPMC K4M, sodium alginate, tamarind seed gum, and carrageenan as mucoadhesive polymers. Results revealed that as the concentration of mucoadhesive polymer increased the mucoadhesive strength increased but gelation temperature decreased. Formulation was optimized on the basis of clarity, pH, gelation temperature, mucoadhesive strength, gel strength, viscosity, drug content, diffusion through sheep nasal mucosa, histopathological evaluation of mucosa, and pharmacodynamic study in rats. Final formulation T5 containing 18% Lutrol F127 and 0.3% PVP K30 was considered as an optimized formulation. T5 released 97.86 ± 0.073% drug in 150 min with a flux of 0.1545 mg cm⁻² min⁻¹ and gelation temperature 31.17 ± 0.30°C. Histopathological evaluation of nasal mucosa revealed that T5 formulation was safe for nasal administration as it caused no damage to nasal epithelium. From the results of pharmacodynamic study, mainly forced swim test (FST), it was concluded that venlafaxine hydrochloride was more effective as an antidepressant by nasal route as in situ gel nasal drops in comparison to oral administration of equivalent dose.Key words: lutrol F127, mucoadhesive, nasal in situ gel, thermoreversible, venlafaxine HCl     

酮洛芬缓释片人体药动学和生物等效性研究

目的:评价受试酮洛芬缓释片与参比酮洛芬片的生物等效性。方法:采用反相高效液相色谱法测定24名健康男性志愿受试者交叉单剂量口服受试酮洛芬缓释片与参比酮洛芬片150mg后血浆中酮洛芬的浓度,用3p97程序进行数据处理。结果:口服受试和参比酮洛芬制荆后的AUC_(0-(?))分别是38.94±9.15μg·h·ml~(-1)、38.04±6.90μg·h·ml~(-1);AUC_(0-(?))分别是44.50±8.09μg·h·ml~(-1)、42.99±8.36μg·h·ml~(-1);T_(max)分别是3.87±0.55 h、1.96±0.60h;C_(max)分别是5.78±1.11μg·ml~(-1)、11.62±2.10μg·ml~(-1);t_(1/2)(Ke)分别是5.88±1.16h、1.70±1.40h。结论:受试酮洛芬缓释片与参比酮洛芬片具有生物等效性。     

Formulation Study and Evaluation of Matrix and Three-layer Tablet Sustained Drug Delivery Systems Based on Carbopols with Isosorbite Mononitrate

The purpose of this research was to develop and evaluate different preparations of sustained delivery systems, using Carbopols as carriers, in the form of matrices and three-layer tablets with isosorbite mononitrate. Matrix tablets were prepared by direct compression whereas three-layer tablets were prepared by compressing polymer barrier layers on both sides of the core containing the drug. The findings of the study indicated that all systems demonstrated sustained release. The properties of the polymer used and the structure of each formulation appear to considerably affect drug release and its release rate. The three-layer formulations exhibit lower drug release compared to the matrices. This was due to the fact that the barrier-layers hindered the penetration of liquid into the core and modified drug dissolution and release. The geometrical characteristics/structure of the tablets as well as the weight/thickness of the barriers-layers considerably influence the rate of drug release and the release mechanisms. Kinetic analysis of the data indicated that drug release from matrices was mainly attributed to Fickian diffusion while three-layer tablets exhibited either anomalous diffusion or erosion/relaxation mechanisms. The advantage of Carbopol formulations is that a range of release profiles can easily be obtained through variations in tablet structure and thus Carbopols are appropriate carriers of oral sustained drug delivery systems for soluble drugs such as the isosorbite mononitrate.     

Development of a Melting Tablet Containing Promethazine HCl Against Motion Sickness

The purpose of this study was to design a 'Traveller Friendly Drug Delivery System' for PM-HCl. Conventional promethazine (PM-HCl) tablets are bitter, need to be taken 1 h before symptoms and water is also needed. Taste-masked granules were produced with Eudragit E100 by extrusion, and analyzed with FTIR, DSC, and XRD. Tablets formulated from granules by direct compression using Ac-Di-Sol, Polyplasdone-XL, Primojel and ion-exchanger Tulsion339 and evaluated for mass uniformity, friability, tensile strength, drug content uniformity, water absorption ratio, in-vitro and in-vivo disintegration time and in-vitro dissolution studies. The observed drug-polymer interactions and reduced crystallinity may be reasons for increased dissolution rates. The formulated tablets were disintegrated within 15 s. Tablets (25 mg PM-HCl) with Ac-Di-Sol (4%) showed complete release within 1 min, while marketed conventional tablets (Phenergan; Rhone-Poulec) release 25% during the same period. A preliminary stability studies for the prepared tablets carried at 30 +/- 2 degrees C/60 +/- 5% RH, and 40 +/- 2 degrees C/75 +/- 5%RH for 3 months showed no significant changes in the tablets quality at 30 +/- 2 degrees C/60 +/- 5% RH. However, at 40 +/- 2 degrees C/75 +/- 5%RH marked increase in in-vitro disintegration time, tensile strength and decrease in friability and water absorption ratio was found. The present studies indicate the abilities of Eudragit E 100 for taste masking and improving the dissolution profile of PM-HCl after complexation. In addition, by employing cost effective direct compression method, fast-dissolving tablets of 400 mg total weight with an acceptable quality could be prepared.     

Guanidine Hydrochloride Denaturation of Glycosylated and Deglycosylated Stem Bromelain

Glycosylation is one of the major naturally occurring covalent modifications of proteins. We have used stem bromelain, a thiol protease with a single, N-glycosylated polypeptide chain as a model to investigate the role of glycosylation of proteins. Periodate oxidation was used to obtain the deglycosylated form of the enzyme. Denaturation studies in the presence of guanidine hydrochloride (Gn·HCl) were performed using fluorescence and circular dichroism spectroscopy. The glycosylated stem bromelain was found to be stabilized by 1.9 kcal/mol as compared to the deglycosylated one. At a given concentration of denaturant, the fraction of denatured protein was higher in the case of deglycosylated stem bromelain. In short, deglycosylated bromelain showed more susceptibility towards guanidine hydrochloride denaturation, indicating the contribution of the carbohydrate part of the glycoprotein to the stability of the enzyme.