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1.
Oral bioavailability of atorvastatin calcium (ATC) is very low (only 14%) due to instability and incomplete intestinal absorption and/or extensive gut wall extraction. When ATC is packed in the form of tablets, powders, etc., it gets destabilized as it is exposed to the oxidative environment, which is usually present during the production process, the storage of the substance, and the pharmaceutical formulation. Therefore, stabilized gastro-retentive floating tablets of ATC were prepared to enhance bioavailability. Water sorption and viscosity measurement studies are performed to get the best polymer matrix for gastro-retention. A 32 factorial design used to prepare optimized formulation of ATC. The selected excipients such as docusate sodium enhanced the stability and solubility of ATC in gastric media and tablet dosage form. The best formulation (F4) consisting of hypromellose, sodium bicarbonate, polyethylene oxide, docusate sodium, mannitol, crosscarmellose sodium, and magnesium stearate, gave floating lag time of 56 ± 4.16 s and good matrix integrity with in vitro dissolution of 98.2% in 12 h. After stability studies, no significant change was observed in stability, solubility, floating lag time, total floating duration, matrix integrity, and sustained drug release rates, as confirmed by DSC and powder X-ray diffraction studies. In vivo pharmacokinetic study performed in rabbits revealed enhanced bioavailability of F4 floating tablets, about 1.6 times compared with that of the conventional tablet (Storvas® 80 mg tablet). These results suggest that the gastric resident formulation is a promising approach for the oral delivery of ATC for improving bioavailability.Key words: atorvastatin calcium, bioavailibility, floating tablets, gastro-retention, stabilization 相似文献
2.
Rehab Mohammad Yusif Irhan Ibrahim Abu Hashim Elham Abdelmonem Mohamed Farid Abd-Elreheim Badria 《AAPS PharmSciTech》2016,17(2):328-338
Currently available anti-ulcer drugs suffer from serious side effects which limited their uses and prompted the need to search for a safe and efficient new anti-ulcer agent. Boswellia gum resin (BR) emerged as a safe, efficient, natural, and economic potential cytoprotective agent. Thus, it is of medical importance to develop gastroretentive (GR) formulations of BR to enhance its bioavailability and anti-ulcer efficacy. Early attempts involved the use of organic solvents and non-applicability to large-scale production. In this study, different tablet formulations were prepared by simple direct compression combining floating and bioadhesion mechanisms employing hydroxypropyl methylcellulose (HPMC), sodium carboxymethyl cellulose (SCMC), pectin (PC), and/or carbopol (CP) as bioadhesive polymers and sodium bicarbonate (SB) as a gas former. The prepared tablets were subjected for assessment of swelling, floating, bioadhesion, and drug release in 0.1 N HCl. The optimized GR formulation was examined for its protective effect on the gastric ulcer induced by indomethacin in albino rabbits compared with lactose tablets. The obtained results disclosed that swelling, floating, bioadhesion, and drug release of the GR tablets of BR depend mainly on the nature of the matrix and the ratio of polymer combinations. Moreover, a combination of SCMC-CP in a ratio of 2:1 (SCP21) exhibited desirable floating, bioadhesion, swelling, and extended drug release. Also, a 6-h pretreatment with SCP21 tablets decreased the severity of inflammation and number of bleeding spots among ulcer-induced rabbits in comparison to those treated with lactose tablets. 相似文献
3.
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
4.
The purpose of this research was to prepare a floating drug delivery system of diltiazem hydrochloride (DTZ). Floating matrix
tablets of DTZ were developed to prolong gastric residence time and increase its bioavailability. Rapid gastrointestinal transit
could result in incomplete drug release from the drug delivery system above the absorption zone leading to diminished efficacy
of the administered dose. The tablets were prepared by direct compression technique, using polymers such as hydroxypropylmethylcellulose
(HPMC, Methocel K100M CR), Compritol 888 ATO, alone or in combination and other standard excipients. Sodium bicarbonate was
incorporated as a gas-generating agent. The effects of sodium bicarbonate and succinic acid on drug release profile and floating
properties were investigated. A 32 factorial design was applied to systematically optimize the drug release profile. The amounts of Methocel K100M CR (X1) and Compritol 888 ATO (X2) were selected as independent variables. The time required for 50% (t50) and 85% (t85) drug dissolution were selected as dependent variables. The results of factorial design indicated that a high level of both
Methocel K100M CR (X1) and Compritol 888 ATO (X2) favors the preparation of floating controlled release of DTZ tablets. Comparable release profiles between the commercial
product and the designed system were obtained. The linear regression analysis and model fitting showed that all these formulations
followed Korsmeyer and Peppas model, which had a higher value of correlation coefficient (r). While tablet hardness had little or no effect on the release kinetics and was found to be a determining factor with regards
to the buoyancy of the tablets.
Published: September 7, 2007 相似文献
5.
Mutalik S Manoj K Reddy MS Kushtagi P Usha AN Anju P Ranjith AK Udupa N 《AAPS PharmSciTech》2008,9(2):651-659
The purpose of this study was to develop a once daily sustained release tablet of aceclofenac using chitosan and an enteric
coating polymer (hydroxypropyl methylcellulose phthalate or cellulose acetate phthalate). Overall sustained release for 24 h
was achieved by preparing a double-layer tablet in which the immediate release layer was formulated for a prompt release of
the drug and the sustained release layer was designed to achieve a prolonged release of drug. The preformulation studies like
IR spectroscopic and differential scanning calorimetry showed the absence of drug–excipient interactions. The tablets were
found within the permissible limits for various physicochemical parameters. Scanning electron microscopy was used to visualize
the surface morphology of the tablets and to confirm drug release mechanisms. Good equivalence in the drug release profile
was observed when drug release pattern of the tablet containing chitosan and hydroxypropyl methylcellulose phthalate (M-7)
was compared with that of marketed tablet. The optimized tablets were stable at accelerated storage conditions for 6 months
with respect to drug content and physical appearance. The results of pharmacokinetic studies in human volunteers showed that
the optimized tablet (M-7) exhibited no difference in the in vivo drug release in comparison with marketed tablet. No significant difference between the values of pharmacokinetic parameters
of M-7 and marketed tablets was observed (p > 0.05; 95% confidence intervals). However the clinical studies in large scale and, long term and extensive stability studies
at different conditions are required to confirm these results. 相似文献
6.
Alginate matrix tablet of diltiazem hydrochloride (DTZ), a water-soluble drug, was prepared using sodium alginate (SAL) and
calcium gluconate (CG) by the conventional wet granulation method for sustained release of the drug. The effect of formulation
variables like SAL/CG ratio, drug load, microenvironmental pH modulator, and processing variable like compression force on
the extent of drug release was examined. The tablets prepared with 1:2 w/w ratio of SAL/CG produced the most sustained release of the drug extending up to 13.5 h. Above and below this ratio, the drug
release was faster. The drug load and the hardness of the tablets produced minimal variation in drug release. The addition
of alkaline or acidic microenvironmental modulators did not extend the release; instead, these excipients produced somewhat
faster release of diltiazem. This study revealed that proper selection of SAL/CG ratio is important to produce alginate matrix
tablet by wet granulation method for sustained release of DTZ. 相似文献
7.
Ahmed Abdelbary Omaima N. El-Gazayerly Nashwa A. El-Gendy Adel A. Ali 《AAPS PharmSciTech》2010,11(3):1058-1067
Trimetazidine dihydrochloride is an effective anti-anginal agent; however, it is freely soluble in water and suffers from a relatively short half-life. To solve this encumbrance, it is a prospective candidate for fabricating trimetazidine extended-release formulations. Trimetazidine extended-release floating tablets were prepared using different hydrophilic matrix forming polymers including HPMC 4000 cps, carbopol 971P, polycarbophil, and guar gum. The tablets were fabricated by dry coating technique. In vitro evaluation of the prepared tablets was performed by the determination of the hardness, friability, content uniformity, and weight variation. The floating lag time and floating duration were also evaluated. Release profile of the prepared tablets was performed and analyzed. Furthermore, a stability study of the floating tablets was carried out at three different temperatures over 12 weeks. Finally, in vivo bioavailability study was done on human volunteers. All tablet formulas achieved <0.5 min of floating lag time, more than 12 h of floating duration, and extended t 1/2. The drug release in all formulas followed zero-order kinetics. T4 and T8 tablets contained the least polymer concentration and complied with the dissolution requirements for controlled-release dosage forms. These two formulas were selected for further stability studies. T8 exhibited longer expiration date and was chosen for in vivo studies. T8 floating tablets showed an improvement in the drug bioavailability compared to immediate-release tablets (Vastrel® 20 mg). 相似文献
8.
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
9.
The aim of the present study was to prepare and characterize extended-release matrix tablets of zidovudine using hydrophilic
Eudragit RLPO and RSPO alone or their combination with hydrophobic ethyl cellulose. Release kinetics was evaluated by using
United States Pharmacopeia (USP)-22 type I dissolution apparatus. Scanning electron microscopy was used to visualize the effect of dissolution medium on matrix
tablet surface. Furthermore, the in vitro and in vivo newly formulated sustained-release zidovudine tablets were compared
with conventional marketed tablet (Zidovir, Cipla Ltd, Mumbai, India). The in-vitro drug release study revealed that either
Eudragit preparation was able to sustain the drug release only for 6 hours (94.3%±4.5% release). Combining Eudragit with ethyl
cellulose sustained the drug release for 12 hours (88.1%±4.1% release). Fitting the in vitro drug release data to Korsmeyer
equation indicated that diffusion along with erosion could be the mechanism of drug release. In vivo investigation in rabbits
showed sustained-release pharmacokinetic profile of zidovudine from the matrix tablets formulated using combination of Eudragits
and ethylcellulose. In conclusion, the results suggest that the developed sustained-release tablets of zidovudine could perform
therapeutically better than conventional dosage forms, leading to improve efficacy and better patient compliance.
Published: January 3, 2006 相似文献
10.
Namfa Sermkaew Kamonthip Wiwattanawongsa Wichan Ketjinda Ruedeekorn Wiwattanapatapee 《AAPS PharmSciTech》2013,14(1):321-331
Novel self-microemulsifying floating tablets were developed to enhance the dissolution and oral absorption of the poorly water-soluble tetrahydrocurcumin (THC). Their physicochemical properties and THC permeability across Caco-2 cell monolayers were assessed. The self-microemulsifying liquid containing THC was adsorbed onto colloidal silicon dioxide, mixed with HPMC, gas-generating agents (sodium bicarbonate and tartaric acid), lactose and silicified-microcrystalline cellulose and transformed into tablets by direct compression. The use of different types/concentrations of HPMC and sodium bicarbonate in tablet formulations had different effects on the floating characteristics and in vitro THC release. The optimum tablet formulation (F2) provided a short floating lag time (∼23 s) together with a prolonged buoyancy (>12 h). About 72% of THC was released in 12 h with an emulsion droplet size in aqueous media of 33.9 ± 1.0 nm while that of a self-microemulsifying liquid was 29.9 ± 0.3 nm. The tablet formulation was stable under intermediate and accelerated storage conditions for up to 6 months. The THC released from the self-microemulsifying liquid and tablet formulations provided an approximately three- to fivefold greater permeability across the Caco-2 cell monolayers than the unformulated THC and indicated an enhanced absorption of THC by the formulations. The self-microemulsifying floating tablet could provide a dosage form with the potential to improve the oral bioavailability of THC and other hydrophobic compounds.KEY WORDS: Caco-2 cells, controlled release, permeability, self-microemulsifying floating tablets, tetrahydrocurcumin 相似文献
11.
Release Mechanisms Behind Polysaccharides-Based Famotidine Controlled Release Matrix Tablets 总被引:1,自引:0,他引:1
Enas M. Elmowafy Gehanne A. S. Awad Samar Mansour Abd El-Hamid A. El-Shamy 《AAPS PharmSciTech》2008,9(4):1230-1239
Polysaccharides, which have been explored to possess gelling properties and a wide margin of safety, were used to formulate
single-unit floating matrix tablets by a direct compression technique. This work has the aim to allow continuous slow release
of famotidine above its site of absorption. The floating approach was achieved by the use of the low density polypropylene
foam powder. Polysaccharides (κ-carrageenan, gellan gum, xyloglucan, and pectin) and blends of polysaccharides (κ-carrageenan
and gellan gum) and cellulose ethers (hydroxypropylmethyl cellulose, hydroxypropylcellulose, sodium carboxymethyl cellulose)
were tried to modulate the release characteristics. The prepared floating tablets were evaluated for their floating behavior,
matrix integrity, swelling studies, in vitro drug release studies, and kinetic analysis of the release data. The differential scanning calorimetry and Fourier transform
infrared spectroscopy studies revealed that changing the polymer matrix system by formulation of polymers blends resulted
in formation of molecular interactions which may have implications on drug release characteristics. This was obvious from
the retardation in drug release and change in its mechanistics. 相似文献
12.
A novel gastro retentive controlled release drug delivery system of verapamil HCl was formulated in an effort to increase
the gastric retention time of the dosage form and to control drug release. Hydroxypropylmethylcellulose (HPMC), carbopol,
and xanthan gum were incorporated for gel-forming properties. Buoyancy was achieved by adding an effervescent mixture of sodium
bicarbonate and anhydrous citric acid. In vitro drug release studies were performed, and drug release kinetics was evaluated using the linear regression method. The optimized
intragastric floating tablet composed of 3:2 of HPMC K4M to xanthan gum exhibited 95.39% drug release in 24 h in vitro, while the buoyancy lag time was 36.2 s, and the intragastric floating tablet remained buoyant for >24 h. Zero-order and
non-Fickian release transport was confirmed as the drug release mechanism from the optimized formulation (F7). X-ray studies
showed that total buoyancy time was able to delay the gastric emptying of verapamil HCl intragastric floating tablet in mongrel
dogs for more than 4 h. Optimized intragastric floating tablet showed no significant change in physical appearance, drug content,
total buoyancy time, or in vitro dissolution pattern after storage at 40°C/75% relative humidity for 3 months. 相似文献
13.
The aim of this investigation was preparation and comparative evaluation of fabricated matrix (FM), osmotic matrix (OM), and
osmotic pump (OP) tablets for controlled delivery of diclofenac sodium (DS). All formulations were evaluated for various physical
parameters, and in vitro studies were performed on USP 24 dissolution apparatus II in pH 7.4 buffer and distilled water. In
vivo studies were performed in 6 healthy human volunteers; the drug was assayed in plasma using HPLC, and results were compared
with the performance of 2 commercial tablets of DS. Various pharmacokinetic parameters (ie, Cmax, Tmax, area under the curve [AUC0–24], and mean residence time) and relative bioavailability were compared. All fabricated formulations showed more prolonged
and controlled DS release compared with commercial tablets studied. The OM and OP tablets, however, performed better than
the matrix tablets. The rate and extent of drug release from FM1 matrix tablets (single polymer) was significantly different
from that of FM2 (admixed polymers). Type of porosigenic agents and osmogens also influenced the drug release. Analysis of
in vitro data by regression coefficient analysis revealed zero-order release kinetics for OM and OP tablets, while FM tablets
exhibited Higuchi kinetics. In vivo results indicated prolonged blood levels with delayed peak and improved bioavailability
for fabricated tablets compared to commercial tablets. It was concluded that the osmotic matrix and osmotic pump tablets could
provide more prolonged, controlled, and gastrointestinal environmental-independent DS release that may result in an improved
therapeutic efficacy and patient compliance. 相似文献
14.
Worawut Kriangkrai Satit Puttipipatkhachorn Pornsak Sriamornsak Thaned Pongjanyakul Srisagul Sungthongjeen 《AAPS PharmSciTech》2014,15(6):1357-1369
Tackiness caused by the gas-entrapped membrane (Eudragit®RL 30D) was usually observed during storage of the effervescent floating tablets, leading to failure in floatation and sustained release. In this work, common anti-tacking agents (glyceryl monostearate (GMS) and talc) were used to solve this tackiness problem. The impact of anti-tacking agent on the properties of free films and corresponding floating tablets was investigated. GMS was more effective than talc in reducing tackiness of the film. Addition and increasing amount of anti-tacking agents lowered the film mechanical strength, but the coating films were still strong and flexible enough to resist the generated gas pressure inside the floating tablet. Wettability and water vapor permeability of the film decreased with increasing level of anti-tacking agents as a result of their hydrophobicity. No interaction between anti-tacking agents and polymer was observed as confirmed by Fourier transform infrared spectroscopy, powder X-ray diffractometry, and differential scanning calorimetry studies. Increasing amount of anti-tacking agents decreased time to float and tended to retard drug release of the floating tablets. Floating properties and drug release were also influenced by type of anti-tacking agents. The obtained floating tablets still possessed good floating properties and controlled drug release even though anti-tacking agent had some effects. The results demonstrated that the tackiness problem of the floating tablets could be solved by incorporating anti-tacking agent into the gas-entrapped membrane.KEY WORDS: anti-tacking agent, coating film, controlled release, effervescent floating tablets, Eudragit®RL 30D 相似文献
15.
Srinivas Mutalik Krishnan Manoj Meka Sreenivasa Reddy Pralhad Kushtagi Achutha Nayak Usha Parambil Anju Averineni Kumar Ranjith Nayanabhirama Udupa 《AAPS PharmSciTech》2008,9(2)
The purpose of this study was to develop a once daily sustained release tablet of aceclofenac using chitosan and an enteric coating polymer (hydroxypropyl methylcellulose phthalate or cellulose acetate phthalate). Overall sustained release for 24 h was achieved by preparing a double-layer tablet in which the immediate release layer was formulated for a prompt release of the drug and the sustained release layer was designed to achieve a prolonged release of drug. The preformulation studies like IR spectroscopic and differential scanning calorimetry showed the absence of drug–excipient interactions. The tablets were found within the permissible limits for various physicochemical parameters. Scanning electron microscopy was used to visualize the surface morphology of the tablets and to confirm drug release mechanisms. Good equivalence in the drug release profile was observed when drug release pattern of the tablet containing chitosan and hydroxypropyl methylcellulose phthalate (M-7) was compared with that of marketed tablet. The optimized tablets were stable at accelerated storage conditions for 6 months with respect to drug content and physical appearance. The results of pharmacokinetic studies in human volunteers showed that the optimized tablet (M-7) exhibited no difference in the in vivo drug release in comparison with marketed tablet. No significant difference between the values of pharmacokinetic parameters of M-7 and marketed tablets was observed (p > 0.05; 95% confidence intervals). However the clinical studies in large scale and, long term and extensive stability studies at different conditions are required to confirm these results.Key words: aceclofenac, chitosan, matrix tablet, pharmacokinetics, sustained release 相似文献
16.
In the present investigation, hydrogenated cottonseed oil (HCSO) was evaluated as a sustained release matrix for a freely
soluble drug, tramadol. Hydrophobic matrix tablets of tramadol, was evaluated by compression of physical mixture of drug and
wax, dispersion of drug in HCSO by hot fusion or solubilisation techniques. The method of preparation of tablet had a significant
effect on drug release with higher release observed from direct compression matrices and slower release from matrix prepared
by dispersion (hot-fused matrices). Influence of addition of hydroxypropylmethyl cellulose, sodium carboxymethyl cellulose,
polyethylene glycol 4000 and surfactants like sodium lauryl sulphate and polysorbate 20 to HCSO matrix on drug release was
investigated. The added excipients exhibited a propensity to enhance drug release from the HCSO matrix. NaCMC was effective
at a lower ratio (<10% w/w) and when incorporated at higher level made HCSO matrix to erode and disintegrate in a short period. 相似文献
17.
The purpose of this research was to study mucoadhesive bilayer buccal tablets of propranolol hydrochloride using the bioadhesive
polymers sodium alginate (Na-alginate) and Carbopol 934P (CP) along with ethyl cellulose as an impermeable backing layer.
The tablets were evaluated for weight variation, thickness, hardness, friability, surface pH, mucoadhesive strength, swelling
index, in vitro drug release, ex vivo drug permeation, ex vivo mucoadhesion, and in vivo pharmacodynamics in rabbits. Tablets
containing Na-alginate and CP in the ratio of 5∶1 (F2) had the maximum percentage of in vitro drug release without disinte-gration
in 12 hours. The swelling index was proportional to Na-alginate content and inversely proportional to CP content. The surface
pH of all tablets was found to be satis-factory (7.0±1.5), close to neutral pH; hence, buccal cavity irritation should not
occur with these tablets. The mechanism of drug release was found to be non-Fickian diffusion and followed zero-order kinetics.
The formulation F4 was optimized based on good biodhesive strength (28.9±0.99 g) and sustained in vitro drug permeation (68.65%±3.69%
for 12 hours). The behavior of formulation F4 was examined in human saliva, and both the drug and the buccal tablet were found
to be stable. The formulation F4 was applied to rabbit oral mucosa for in vivo studies. The formulation inhibited isoprenaline-induced
tachycardia. The studies conducted in rabbits confirmed the sustained release as compared with intravenous administration.
Published: September 21, 2007 相似文献
18.
The purpose of research was to develop a mucoadhesive multiparticulate sustained drug delivery system of pravastatin sodium,
a highly water-soluble and poorly bioavailable drug, unstable at gastric pH. Mucoadhesive microparticles were formulated using
eudragit S100 and ethyl cellulose as mucoadhesive polymers. End-step modification of w/o/o double emulsion solvent diffusion
method was attempted to improve the purity of the product, that can affect the dose calculations of sustained release formulations
and hence bioavailability. Microparticles formed were discrete, free flowing, and exhibited good mucoadhesive properties.
DSC and DRS showed stable character of drug in microparticles and absence of drug polymer interaction. The drug to polymer
ratio and surfactant concentration had significant effect on mean particle size, drug release, and entrapment efficiency.
Microparticles made with drug: eudragit S100 ratio of 1:3 (F6) exhibited maximum entrapment efficiency of 72.7% and ex vivo mucoadhesion time of 4.15 h. In vitro permeation studies on goat intestinal mucosa demonstrated a flux rate (1,243 μg/cm2/h) that was 169 times higher than the flux of pure drug. The gastric instability problem was overcome by formulating the
optimized microparticles as enteric-coated capsules that provided a sustained delivery of the highly water-soluble drug for
12 h beyond the gastric region. The release mechanism was identified as fickian diffusion (n = 0.4137) for the optimized formulation F6. Conclusively, a drug delivery system was successfully developed that showed delayed
and sustained release up to 12 h and could be potentially useful to overcome poor bioavailability problems associated with
pravastatin sodium. 相似文献
19.
A multiple-unit-type oral floating dosage form (FDF) of 5-fluorouracil (5-FU) was developed to prolong gastric residence time,
target stomach cancer, and increase drug bioavailability. The floating bead formulations were prepared by dispersing 5-FU
together with calcium carbonate into a mixture of sodium alginate and hydroxypropyl methylcellulose solution and then dripping
the dispersion into an acidified solution of calcium chloride. Calcium alginate beads were formed, as alginate undergoes ionotropic
gelation by calcium ions and carbon dioxide develops from the reaction of carbonate salts with acid. The evolving gas permeated
through the alginate matrix, leaving gas bubbles or pores, which provided the beads buoyancy. The prepared beads were evaluated
for percent drug loading, drug entrapment efficiency, image, surface topography, buoyancy, and in vitro release. The formulations
were optimized for different weight ratios of gas-forming agent and sodium alginate. The beads containing higher amounts of
calcium carbonate demonstrated instantaneous, complete, and excellent floating ability over a period of 24 hours. The optimized
formulation was subjected to in vivo antitumor studies to check the therapeutic efficacy of the floating dosage forms containing
5-FU against benzo(a)pyrene-induced stomach tumors in albino female mice (Balb/C strain). The multiple-bead FDF was found
to reduce the tumor incidence in mice by 74%, while the conventional tablet dosage form reduced this incidence by only 25%.
Results indicate that FDF performed significantly better than the simple tablet dosage form.
Published: June 22, 2007 相似文献
20.
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