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1.
Meka Lingam Thadisetty Ashok Vobalaboina Venkateswarlu Yamsani Madhusudan Rao 《AAPS PharmSciTech》2008,9(4):1253-1261
A biphasic gastroretentive floating drug delivery system with multiple-unit mini-tablets based on gas formation technique
was developed to maintain constant plasma level of a drug concentration within the therapeutic window. The system consists
of loading dose as uncoated core units, and prolonged-release core units are prepared by direct compression process; the latter
were coated with three successive layers, one of which is seal coat, an effervescent (sodium bicarbonate) layer, and an outer
polymeric layer of polymethacrylates. The formulations were evaluated for quality control tests, and all the parameters evaluated
were within the acceptable limits. The system using Eudragit RL30D and combination of them as polymeric layer could float
within acceptable time. The drug release was linear with the square root of time. The rapid floating and the controlled release
properties were achieved in this present study. When compared with the theoretical release profile, the similarity factor
of formulation with coating of RS:RL (1:3)–7.5%, was observed to be 74, which is well fitted into zero-order kinetics confirming
that the release from formulation is close to desired release profile. The stability samples showed no significant change
in dissolution profiles (p > 0.05). In vivo gastric residence time was examined by radiograms, and it was observed that the units remained in the stomach for about 5 h. 相似文献
2.
Ramji Anil Kumar Arza Chandra Sekhara Rao Gonugunta Prabhakar Reddy Veerareddy 《AAPS PharmSciTech》2009,10(1):220-226
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®. 相似文献
3.
The purpose of this research was to prepare a gastroretentive drug delivery system of ranitidine hydrochloride. Guar gum,
xanthan gum, and hydroxypropyl methylcellulose were evaluated for gel-forming properties. Sodium bicarbonate was incorporated
as a gas-generating agent. The effects of citric acid and stearic acid on drug release profile and floating properties were
investigated. The addition of stearic acid reduces the drug dissolution due to its hydrophobic nature. A 32 full factorial design was applied to systemically optimize the drug release profile. The amounts of citric acid anhydrous
(X1) and stearic acid (X2) were selected as independent variables. The times required for 50% (t50) and 80% drug dissolution (t80), and the similarity factor f2 were selected as dependent variables. The results of the full factorial design indicated that a low amount of citric acid
and a high amount of stearic acid favors sustained release of ranitidine hydrochloride from a gastroretentive formulation.
A theoretical dissolution profile was generated using pharmacokinetic parameters of ranitidine hydrochloride. The similarity
factor f2 was applied between the factorial design batches and the theoretical dissolution profile. No significant difference was observed
between the desired release profile and batches F2, F3, F6, and F9. Batch F9 showed the highest f2 (f2=75) among all the batches,
and this similarity is also reflected in t50 (∼214 minutes) and t80 (∼537 minutes) values. These studies indicate that the proper balance between a release rate enhancer and a release rate
retardant can produce a drug dissolution profile similar to a theoretical dissolution profile. 相似文献
4.
Swati C. Jagdale Amit J. Agavekar Sudhir V. Pandya Bhanudas S. Kuchekar Aniruddha R. Chabukswar 《AAPS PharmSciTech》2009,10(3):1071-1079
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. 相似文献
5.
A gastro retentive floating drug delivery system with multiple-unit minitab’s based on gas formation technique was developed
in order to prolong the gastric residence time and to increase the overall bioavailability of the drug. The system consists
of the drug-containing core units prepared by direct compression process, which are coated with three successive layers of
an inner seal coat, effervescent layer (sodium bicarbonate) and an outer gas-entrapped polymeric membrane of an polymethacrylates
(Eudragit RL30D, RS30D, and combinations of them). Only the system using Eudragit RL30D and combination of them as a gas-entrapped
polymeric membrane could float. The time to float decreased as amount of the effervescent agent increased and coating level
of gas-entrapped polymeric membrane decreased. The optimum system floated completely within 3 min and maintained the buoyancy
over a period of 12 h. The drug release was controlled and linear with the square root of time. Increasing coating level of
gas-entrapped polymeric membrane decreased the drug release. Both the rapid floating and the controlled release properties
were achieved in the multiple-unit floating drug delivery system developed in this present study. The analysis of the parameter
dissolution data after storage at 40 °C and 75% RH for 3 months showed, no significant change indicating the two dissolution
profiles were considered to be similar (f2 value is more than 50). 相似文献
6.
Atul C. Badhan Rajashree C. Mashru Punit P. Shah Arti R. Thakkar Nitin B. Dobaria 《AAPS PharmSciTech》2009,10(2):459-467
In the present work, sustained release gastroretentive minimatrices of amoxicillin have been designed and optimized using
central composite design. Effect of amount of xanthan gum, rate controlling polymers (HPMC K100M CR/PEO coagulant (1:1)),
carbopol 974P, and gas generating couple (sodium bicarbonate/citric acid (3:1)) was studied on dependent (response) variables,
i.e., buoyancy lag time, drug release at 1 h, time required for 95% drug release, swelling index, and bioadhesive strength.
Minimatrices were prepared by non aqueous granulation method using solution of PVP K30 in isopropyl alcohol. All the formulations
were found to contain 99.2% to 100.9% of amoxicillin per minimatrix. Optimum formulation (Formulation number AGT09) containing
high level of the independent variables was having buoyancy lag time of 7 min and drug release at 1 h was 32.5%. It required
9.39 h for 95% drug release while swelling index and bioadhesive strength were 341 and 17.9 dyn/cm2, respectively. This formulation was said to be optimum because it has minimum buoyancy lag time, requires maximum time for
95% drug release, and has higher bioadhesive capabilities. In vitro results of an optimized formulation indicate its sustained drug release and gastric retention capability, which may be very
useful for effective treatment of H. pylori infection. 相似文献
7.
聚乙二醇-聚乳酸嵌段共聚物在药物递送系统中的应用 总被引:1,自引:0,他引:1
聚乙二醇-聚乳酸嵌段共聚物具备良好的生物相容性和生物可降解性,是良好的纳米级药物载体。嵌段共聚物具有载药能力强、粒径小、体内循环时间长、主动靶向性和被动靶向性等特点,因此在药物递送系统中得到广泛应用。简要介绍了聚乙二醇-聚乳酸嵌段共聚物的合成和性质,及其作为脂质体、胶束、微球等载体在药物递送系统中的最新进展。 相似文献
8.
Superoxide dismutase (SOD) has demonstrated therapeutic potential for treating a variety of conditions including radiation injury, oxygen toxicity, reperfusion injury, and inflammation, especially arthritis. However, the native enzyme's short half-life in plasma (6 minutes in mice. 25 minutes in man) limits the enzyme's effectiveness in many applications, or requires infusion of large doses. High doses of SOD derived from either natural or rDNA sources may increase the potential for immunologic sensitization. One effective use of native SOD is intra particular administration for treatment of arthritis, where injection of SOD into joints retards elimination (15 hour terminal half-life), allowing the effective use of lower doses.
To overcome the limitations resulting from rapid clearance. various researchers have increased the persistence of SOD by cross-linking SOD or by attaching polymeric substances, including dextrans, albumin, Ficoll, polyvinyl alcohol or polyethylene glycol (PEG). PEG is relatively safe; however. the amount of modification by PEG. is the MW range 1.900-5.000 daltons, which is necessary to optimally increase serum persistence and reduce immunogenicity, results in the loss of much of the enzymatic activity.
In this report we describe the preparation of SOD adducts containing I to 4 strands of high MW PEG (41,000-72,000 daltons). The MW range of these adducts, measured by steric exclusion HPLC based on protein standards, is 200,000 to over 1,100,000 daltons. The number of PEG strands attached per SOD dimer (32,000 daltons) was measured by HPLC. Because of the low degree of protein modification required to produce very high MW products, these PEG-SODS retain 90%-100% of the SOD activity of the native enzyme. Additionally, these very large adducts demonstrate longer persistence and lower immunogenicity and antigenicity compared to the more highly modified PEG-SODS containing low MW PEG (i.e., 7-16 strands of 5.000 dalton methoxy-PEG). 相似文献
To overcome the limitations resulting from rapid clearance. various researchers have increased the persistence of SOD by cross-linking SOD or by attaching polymeric substances, including dextrans, albumin, Ficoll, polyvinyl alcohol or polyethylene glycol (PEG). PEG is relatively safe; however. the amount of modification by PEG. is the MW range 1.900-5.000 daltons, which is necessary to optimally increase serum persistence and reduce immunogenicity, results in the loss of much of the enzymatic activity.
In this report we describe the preparation of SOD adducts containing I to 4 strands of high MW PEG (41,000-72,000 daltons). The MW range of these adducts, measured by steric exclusion HPLC based on protein standards, is 200,000 to over 1,100,000 daltons. The number of PEG strands attached per SOD dimer (32,000 daltons) was measured by HPLC. Because of the low degree of protein modification required to produce very high MW products, these PEG-SODS retain 90%-100% of the SOD activity of the native enzyme. Additionally, these very large adducts demonstrate longer persistence and lower immunogenicity and antigenicity compared to the more highly modified PEG-SODS containing low MW PEG (i.e., 7-16 strands of 5.000 dalton methoxy-PEG). 相似文献
9.
《Free radical research》2013,47(1):553-562
Superoxide dismutase (SOD) has demonstrated therapeutic potential for treating a variety of conditions including radiation injury, oxygen toxicity, reperfusion injury, and inflammation, especially arthritis. However, the native enzyme's short half-life in plasma (6 minutes in mice. 25 minutes in man) limits the enzyme's effectiveness in many applications, or requires infusion of large doses. High doses of SOD derived from either natural or rDNA sources may increase the potential for immunologic sensitization. One effective use of native SOD is intra particular administration for treatment of arthritis, where injection of SOD into joints retards elimination (15 hour terminal half-life), allowing the effective use of lower doses.To overcome the limitations resulting from rapid clearance. various researchers have increased the persistence of SOD by cross-linking SOD or by attaching polymeric substances, including dextrans, albumin, Ficoll, polyvinyl alcohol or polyethylene glycol (PEG). PEG is relatively safe; however. the amount of modification by PEG. is the MW range 1.900–5.000 daltons, which is necessary to optimally increase serum persistence and reduce immunogenicity, results in the loss of much of the enzymatic activity.In this report we describe the preparation of SOD adducts containing I to 4 strands of high MW PEG (41,000–72,000 daltons). The MW range of these adducts, measured by steric exclusion HPLC based on protein standards, is 200,000 to over 1,100,000 daltons. The number of PEG strands attached per SOD dimer (32,000 daltons) was measured by HPLC. Because of the low degree of protein modification required to produce very high MW products, these PEG-SODS retain 90%-100% of the SOD activity of the native enzyme. Additionally, these very large adducts demonstrate longer persistence and lower immunogenicity and antigenicity compared to the more highly modified PEG-SODS containing low MW PEG (i.e., 7–16 strands of 5.000 dalton methoxy-PEG). 相似文献
10.
RH Fahmy 《AAPS PharmSciTech》2012,13(3):990-1004
Multiparticulate floating drug delivery systems have proven potential as controlled-release gastroretentive drug delivery systems that avoid the "all or none" gastric emptying nature of single-unit floating dosage forms. An objective of the presence investigation was to develop calcium silicate (CaSi)/calcium alginate (Ca-Alg)/hydroxypropyl methylcellulose (HPMC) mucoadhesive-floating beads that provide time- and site-specific drug release of alfuzosin hydrochloride (Alf). Beads were prepared by simultaneous internal and external gelation method utilizing 3(2) factorial design as an experimental design; with two main factors evaluated for their influence on the prepared beads; the concentration of CaSi as floating aid (X (1)) and the percentage of HPMC as viscosity enhancer and mucoadhesive polymer (X (2)), each of them was tested in three levels. Developed formulations were evaluated for yield, entrapment efficiency, particle size, surface topography, and buoyancy. Differential scanning calorimetry, Fourier transform infrared spectroscopy, in vitro drug release, as well as in vitro mucoadhesion using rat stomach mucosal membrane were also conducted. Percentage yield and entrapment efficiency ranged from 57.03% to 78.51% and from 49.78% to 83.26%, respectively. Statistical analysis using ANOVA proved that increasing the concentration of either CaSi or HPMC significantly increased the beads yield. Both CaSi and HPMC concentrations were found to significantly affect Alf release from the beads. Additionally, higher CaSi concentration significantly increased the beads diameter while HPMC concentration showed significant positive effect on the beads mucoadhesive properties. CaSi/Ca-Alg/HPMC beads represent simple floating-mucoadhesive gastroretentive system that could be useful in chronopharmacotherapy of benign prostatic hyperplasia. 相似文献
11.
生物可降解聚合物纳米粒给药载体 总被引:4,自引:0,他引:4
生物可降解聚合物纳米粒用于给药载体具有广阔的前景。本文综述了生物可降解聚合物纳米粒给药载体领域的最新进展 :包括纳米粒表面修饰特性、药物释放、载多肽和蛋白质等生物大分子药物传输中的潜在应用。 相似文献
12.
M. Basri A. B. Salleh K. Ampon W. M. Z. Yunus C. N. A. Razak 《Biocatalysis and Biotransformation》1991,4(4):313-317
Lipase was modified using polyethylene glycol activated by p-nitrochloroformate. The hydrolytic activity of the polyethylene glycol-derivatised lipase (PEG-lipase) was relatively low compared with that of the unmodified enzyme in aqueous system. The esterification activity, however, was enhanced following the modification. The rate of esterification of butyric acid was higher than that of oleic acid. Benzene was the best solvent for the esterification reaction. 相似文献
13.
The purpose of this research was to develop the hydrodynamically balanced delivery system of Clarithromycin (CLA) which, after
oral administration should have the ability to prolong gastric residence time with the desired in vitro release profile for the localized action in the stomach, in the treatment of Helicobacter pylori (H.pylori) mediated peptic ulcer. By applying wet granulation technique floating tablets of Clarithromycin were prepared.
The proportion of sodium bicarbonate was varied to get the least possible lag time, also the polymer part varied to get the
desired release. In vivo radiographic studies were performed with Barium sulphate loaded formulation to justify the increased gastric residence time
of the dosage form in the stomach, based on the floating principle. The formulation developed using 66.2% Clarithromycin,
12% HPMC K4M polymer, 8% sodium bicarbonate gave floating lag time less than 3 min with a floating time of 12 h, and an in vitro release profile very near to the desired release. X-ray studies showed the enhanced gastric residence time of the tablet
to 220 ± 30 min. The mechanism of release of Clarithromycin from the floating tablets is anomalous diffusion transport and
follows zero order kinetics. In vivo radiographic studies suggest that the tablet has increased gastric residence time for the effective localized action of the
antibiotic (Clarithromycin) in the treatment of H.pylori mediated peptic ulcer. 相似文献
14.
An aqueous two-phase system of dextran and polyethylene glycol was investigated as a reaction medium for pig liver microsomes in order to find out if the partition of the microsomes, of the substrate 7-ethoxycoumarin and of the product 7-hydroxycoumarin favoured any biotechnological perspectives. Cytochrome-P-450 and NADPH-cytochrome P-450 reductase concentrations and the monooxygenase 7-ethoxycoumarin deethylation activity were measured under a variety of the system parameters. Microsomes totally partition into the bottom phase whereas the concentration ratio of substrate to product is higher in the microsome free top phase. An unfavourable effect is the specific partial deactivation of the cytochrome P-450 by polyethylene glycol. 相似文献
15.
V. I. Yelinova A. A. Bobko D. G. Mazhukin A. L. Markel V. V. Khramtsov 《Russian Journal of Bioorganic Chemistry》2003,29(4):395-401
The synthesis of new donors and acceptors of nitrogen oxide is described. New lipophilic nitronylnitroxyl radicals (NNR) that act as paramagnetic scavengers of nitrogen oxide are synthesized and characterized. The purity of the preparations is determined, and their structures are confirmed. The lipophilicity of the radicals is tested by ESR spectroscopy. The incorporation into lipid multilayers is shown to protect NNR from reduction in biological samples, while their ability to scavenge nitrogen oxide and form iminonitroxyl radicals is retained. A decreased rate of NNR reduction under these conditions substantially enhances their effectiveness as paramagnetic acceptors of nitrogen oxide in biological systems. The synthesis of a new hydrophilic NO donor, 3-bromo-3,4-dihydro-4,4-dimethyl-3-(2-pyridyl)-diazet-1,2-dioxide (DDpyr), is described. The constants of DDpyr decomposition in tris-HCl buffer (pH 7.5) and in DMSO are determined (4.5 × 10–6 and 0.5 × 10–6 s–1, respectively). A substantially higher rate of DDpyr decomposition in buffer, compared with the decomposition rates determined previously for some diazetines, makes DDpyr a prospective candidate for the use in aqueous media. It is found in experiments on perfused rat caudal artery that DDpyr is an effective vasodilator. Intraperitoneal injection of DDpyr to hereditarily hypertensive rats (ISIAH line) at doses of 100–200 g/kg body mass considerably diminishes their systolic arterial pressure. 相似文献
16.
一种用聚乙二醇制备微粒体的方法 总被引:8,自引:0,他引:8
介绍一种用聚乙二醇(PEG)制备微粒体的方法.大鼠肝匀浆经聚乙二醇-6000凝聚,及两次高速离心即可得到微粒体组分,与超速离心方法比较,可省去超速离心步骤,又缩短了分离制备的时间,是一种比较简单易行的方法. 相似文献
17.
Jochen Weiss Eric A. Decker D. Julian McClements Kristberg Kristbergsson Thrandur Helgason Tarek Awad 《Food biophysics》2008,3(2):146-154
The inclusion of bioactive compounds, such as carotenoids, omega-3 fatty acids, or phytosterols, is an essential requisite
for the production of functional foods designed to improve the long-term health and well-being of consumers worldwide. To
incorporate these functional components successfully in a food system, structurally sophisticated encapsulation matrices have
to be engineered, which provide maximal physical stability, protect ingredients against chemical degradation, and allow for
precise control over the release of encapsulated components during mastication and digestion to maximize adsorption. A novel
encapsulation system initially developed in the pharmaceutical industries to deliver lipophilic bioactive compounds is solid
lipid nanoparticles (SLN). SLN consist of crystallized nanoemulsions with the dispersed phase being composed of a solid carrier
lipid–bioactive ingredient mixture. Contrary to larger colloidal solid lipid particles, specific crystal structures can be
“dialed-in” in SLN by using specific surfactant mixtures and ensuring that mean particle sizes are below 100–200 nm. Moreover,
in SLN, microphase separations of the bioactive compound from the solidifying lipid matrix can be prevented resulting in an
even dispersion of the encapsulated compound in the solid matrix thereby improving chemical and physical stability of the
bioactive. In this review article, we will briefly introduce the structure, properties, stability, and manufacturing of solid
lipid particles and discuss their emerging use in food science. 相似文献
18.
聚乙二醇对菠萝蛋白酶的化学修饰 总被引:5,自引:0,他引:5
方法:用琥珀酸酐法活化的聚乙二醇对菠萝蛋白酶进行化学修饰,得到菠萝蛋白酶的修饰酶,对比研究三种菠萝蛋白酶:修饰酶、混合酶、天然酶的热稳定性及酸碱稳定性,考察金属离子对三种菠萝蛋白酶的影响。结果:当在55℃水浴保温100min后天然酶活力只保留20%,混合酶活力保留37%,修饰酶活力保留58%;在pH3.0-4.5及pH6.0-7.0的条件下,修饰酶活力高于天然酶活力。当Ca2 的浓度达到0.05mg/mL时,修饰酶的活力高达257.66%;当Mg2 的浓度达到0.035mg/mL时,修饰酶的活力高达147.25%。一价离子Na 对三种菠萝蛋白酶无明显影响。结论:修饰的菠萝蛋白酶对温度和pH值的稳定性均比天然酶有很大程度的提高。混合酶的活力介于天然酶和修饰酶之间说明聚乙二醇对菠萝蛋白酶有一定的保护作用。二价离子Ca2 、Mg2 对三种菠萝蛋白酶活力均有不同程度的激活作用。 相似文献
19.
目的探讨用聚乙二醇(polyethylene glycol,PEG)溶液分离富集miRNA的操作方法和分离富集效果,并与Ambion公司的miRNA分离试剂盒分离效果进行比较。方法用PEG溶液和Ambion公司的miRNA分离试剂盒从肝脏组织总RNA中分离富集miRNA,用变性琼脂糖和变性聚丙烯酰胺凝胶电泳鉴定分离效果,并在富集的miRNA中用RT—PCR扩增miR-122以鉴定是否有效地回收了miRNA。结果PEG和Ambion公司的miRNA分离试剂盒都能有效地富集miRNA,PEG富集的RNA片段比Ambion公司的试剂盒的大。结论PEG溶液能有效地分离富集miRNA,和Ambion公司的miRNA分离试剂盒分离效果相当,并具有操作简便、快捷及成本低廉的优点。 相似文献
20.
The ability of self-emulsifying drug delivery systems (SEDDS) to improve solubility, dissolution rate and bioavailability
of a poorly water-soluble calcium channel blocker, nimodipine (NM) was evaluated in the present investigation. Solubility
of NM in various oils, surfactants and cosurfactants was determined. The influence of the ratio of oil to surfactant + cosurfactant,
pH of aqueous phase on mean globule size of resulting emulsions was studied by means of photon correlation spectroscopy. The
NM loaded SEDDS selected for the in vitro and in vivo studies exhibited globule size less than 180 nm. In vitro dissolution studies indicated that NM loaded SEDDS could release complete amount of NM irrespective of the pH of the dissolution
media. Pharmacokinetics of NM suspension, NM oily solution, NM micellar solution and NM SEDDS were evaluated and compared
in rabbits. Relative bioavailability of NM in SEDDS was significantly higher than all the other formulations. NM loaded SEDDS
were subjected to various conditions of storage as per ICH guidelines for 3 months. NM SEDDS successfully withstood the stability
testing. 相似文献