SR Tablets Research Articles

Bioavailability and pharmacokinetic study of Metformin 500 mg tablet (SR formulations) in healthy human volunteers

Bioavailability and Bioequivalence studies have become an important part of the clinical research in India. This study was performed to find out the safety and efficacy of two Metformin 500 mg tablet (SR formulations). This study was an open label, balanced, randomized, two treatment, two periods, two sequences, single dose, cross over bioequivalence study under fasting condition. Metformin Hydrochloride (SR) 500 mg tablet was the Test formulation and Dibeta SR tablet [containing Metformin Hydrochloride (SR) 500 mg] was the Reference standard. Volunteers were randomly given a single oral dose of the test and the reference formulation under fasting condition, with a washout period of 07 days. Drug concentration in the plasma samples were quantified by using a validated method on LC/MS/MS. Win Nonlin Version 5.2 software was used for statistical calculations. Cmax, AUC0-t and AUC0-∞ values of the test formulation and reference standard were 89.13%, 87.46%, 88.29%, and 112.44%, 123.85% and 123.87%, respectively. Cmax, AUC0-t and AUC0- ∞ values of the test formulation and reference standard fall within the acceptable range of 80–125%. So, the present study concludes that the test formulation is bioequivalent to the reference standard.

Development of An Antidiabetic Phytocomposite Loaded Phytoceutical Formulation, Its Quality Control and Pharmacokinetic Studies and Establishing In Vitro- In Vivo Correlation

This study reports the development of solid oral phytoceutical formulations with Phytocomposite (PHC), an antidiabetic poly herbal preparation as the active core material. Spherical, monolithic PHC microspheres of size range (10 -100 µm) were obtained with Hausner ratio, Carr’s index and angle of repose of 1.141± 0.010, 12.418±0.769 and 25.17±0.96 respectively. Encapsulation efficiency amongst different batches (F1-F5) ranged from 96.8- 100.7, with 99% release profile up to 12h. Conventional and sustained release tablets were prepared by direct compression and compatibility amongst polymers and the PHC checked by FTIR studies. Natural polymers viz. gum kondagogu, gum karaya, Aegle marmelos gum were used as release retardant. Optimized batch of conventional tablets (F6) showed 99.8 % release in 35 min and optimized batch of PHC-SR tablets (F12) showed 99.9% release at 12th hr, both followed zero order kinetics and non-Fickian diffusion. These optimized formulations were subjected to stability studies and the similarity factors (f2) of the conventional and SR tablets were 88.75 and 66.76 respectively. Pharmacokinetic parameters of three formulations in rat plasma were analyzed by PK Solver 2.0. In vitro-in vivo correlation (IVIVC) of three different formulations showed Level A correlation in all cases.

Development and evaluation of Ketoprofen sustained release matrix tablet using Hibiscus rosa-sinensis leaves mucilage

Currently, the use of natural gums and mucilage is of increasing importance in pharmaceutical formulations as valuable drug excipient. Natural plant-based materials are economic, free of side effects, biocompatible and biodegradable. Therefore, Ketoprofen matrix tablets were formulated by employing Hibiscus rosa-sinensis leaves mucilage as natural polymer and HPMC (K100M) as a synthetic polymer to sustain the drug release from matrix system. Direct compression method was used to develop sustained released matrix tablets. The formulated matrix tablets were evaluated in terms of physical appearance, weight variation, thickness, diameter, hardness, friability and in vitro drug release. The difference between the natural and synthetic polymers was investigated concurrently. Matrix tablets developed from each formulation passed all standard physical evaluation tests. The dissolution studies of formulated tablets revealed sustained drug release up to 24h compared to the reference drug Apo Keto® SR tablets. The dissolution data later were fitted into kinetic models such as zero order equation, first order equation, Higuchi equation, Hixson Crowell equation and Korsmeyer-Peppas equation to study the release of drugs from each formulation. The best formulations were selected based on the similarity factor (f2) value of 50% and more. Through the research, it is found that by increasing the polymers concentration, the rate of drug release decreased for both natural and synthetic polymers. The best formulation was found to be F3 which contained 40% Hibiscus rosa-sinensis mucilage polymer and showed comparable dissolution profile to the reference drug with f2 value of 78.03%. The release kinetics of this formulation has shown to follow non-Fickian type which involved both diffusion and erosion mechanism. Additionally, the statistical results indicated that there was no significant difference (p>0.05) between the F3 and reference drug in terms of MDT and T50% with p-values of 1.00 and 0.995 respectively.

Study of pharmacotherapy role in smoking cessation giving an insight into the frequency of smoking among Zagazig University Hospitals’ staff in 2013

Background“Smoking is the main avoidable cause of death around the world”. It’s prevalence is about one billion smokers in the global adult population. “The most cost effective and well-documented methods for smoking cessation are professional advice combined with the nicotine replacement therapy”. So the main aim of hospital staff must be to give advices about smoking cessation and the ways to it. The aim of this work was to study the pharmacotherapy role in smoking cessation giving an insight into the frequency of smoking among Zagazig University Hospitals’ staff in 2013. Subjects and methodsThis epidemiological, observational and prospective study was carried out at Zagazig University Hospitals from the period January 2013 to December 2013. Subjects150 of those current smokers agreed to answer the study questionnaire and share in this study. The included subjects were 144 males and 6 females with a mean age of 39.48±11.95years. MethodsThe studied subjects were subjected to the following: (1) personal history including: smoking history and family history, (2) routine investigations and (3) plain X-ray. The studied subjects (150) were divided into 2 groups according to their agreement for taking pharmacotherapy: group I: included 111 subjects treated by behavioral therapy alone for 3months. Group II: included 39 subjects treated by behavioral therapy plus pharmacotherapy (Bupropion SR tablet) for 3months. ResultsA statistically highly significant percentage of subjects who did previous trial of quitting was found in group II than that in group I. Also, there was a statistically highly significant percentage of subjects who are less nicotine dependent in group II than that in group I, but the reverse was present in highly nicotine dependent subjects according to Fagerstrom score. The final outcome of quitting trial with a successful cessation rate was 48%, while the failed cessation rate was 52% and there was a statistically significant higher successful rate in group II (69.3%) than that in group I (40.5%). As regards occupation, the physicians had statistically highly significant higher levels of successful rate than para-medicals who had high levels of failed cessation rate. A statistically highly significant increase in the percentage of other smoker family member was found in failed cessation group than that in successful cessation one. Regarding Fagerstrom score, there were statistically significant increases in percentage of subjects who were less nicotine dependent in successful cessation group than that in failed cessation one and also in percentage of subjects who were highly nicotine dependent in failed cessation group than that in successful one. Conclusion(1) Programs promoting smoking cessation including behavioral therapy in addition to the complementary role of pharmacotherapy (Bubropion SR) enhanced the chance of success in smoking cessation. (2) This pilot study (regarding the number of the studied individuals) pointed to the smoking dilemma in a locality where smoking behavior should be brought to a minimum especially among physicians.

Optimization of elastic transfersomes formulations for transdermal delivery of pentoxifylline

Pentoxifylline (PTX) is a xanthine derivative indicated in treatment of intermittent claudication and chronic occlusive arterial diseases. It has low oral bioavailability and short half-life; thus, it was considered as a good candidate drug for the transdermal transfersomes formulation. In the present study, an attempt has been made for development, in-vitro and in-vivo evaluation of transdermal transfersomes using sodium cholate (SC) and non-ionic surfactants as edge activators. The optimal formulation, F4(Gcholate), exhibited drug entrapment efficiency of 74.9±1.6%, vesicles elasticity of 145±0.6 (mgs−1cm−2), zeta potential of −34.9±2.2mV, average vesicle diameter of 0.69±0.049μm with PDI of 0.11±0.037 and permeation flux of 56.28±0.19μgcm−2h−1. It attained a prolonged drug release where 79.1±2.1% of PTX released after 10h of the run. The drug release kinetic obeys Higuchi model (R2=0.997) with Fickian diffusion mechanism. Moreover, the formula enhanced drug permeation through the excised rat’s skin predominantly via the carrier-mediated mechanism by 9.1 folds in comparison with the control. Results of the in vivo pharmacokinetics study in male volunteers showed that F4(Gcholate) transfersomes formulation increased PTX absorption and prolonged its half-life comparing to the commercial oral SR tablets. Hence, the elastic transfersomes formulation of PTX possesses admirable potential to avoid drug metabolism, improve PTX bioavailability and sustain its release.

Modified Release of Metformin Hydrochloride using Ion Exchange Resin Complex in Floating Mucoadhesive Tablets

Background: Metformin hydrochloride (HCl) is an oral antihyperglycemic drug used in the management of type 2 diabetes. Metformin HCl is not chemically or pharmacologically related to any other classes of oral antihyperglycemic agents and very successfully used as drug of first choice. It has 50-60% oral bioavailability.It is believed to be predominantly absorbed in the upper part of the intestine, and estimated time for its complete absorption is approximately 6 h. Clinical trials with metformin have demonstrated decreased bioavailability at higher doses, suggesting saturable intestinal absorption. There is need and scope to increase oral bioavailability of metformin HCl. These details led to an idea of development of SR tablet with more gastric/duodenum retention and was designed as SR tablet using ion exchange principle in floating, mucoadhesive matrix. Aim: The objective of this research was to formulate floating mucoadhesive tablet of metformin HCl in complex with ion exchange resin, for the therapeutic dose of 250 mg. Materials and Medhods: Metformin HCl being cationic drug can be complexed with cation exchange resin like indion 244.This study began with formulation and optimization of drug-resin complex (DRC). Various parameters like the use of batch and column process, complexation time, temperature, and pH were studied and optimized. DRC was characterized by infrared spectroscopy and X-ray diffraction pattern. The efficient drug loading was evident in a batch process using activated indion 244 with a drug-resin ratio of 1:1. Drug complexation enhanced with pH 3.5, temperature 60°C. Infrared spectroscopy revealed complexation of: −NH group of the drug with −C=O stretching of aryl acids of indion 244. Optimized DRC obtained was amorphous in nature. This DRC was put into tablet which could sustain the release of metformin in the favorable region of gastric pH because of inherent slow release from DRC along with a matrix of hydroxylpropylmethylcellulose (HPMC) K100M and Carbopol 974P. HPMC K100M along with sodium bicarbonate made this tablet float and Carbopol 974P gave the additional property of mucoadhesion. The quantity of carbopol optimized first and quantity of HPMC and carbopol using 32 factorial design. Results: The tablets were evaluated for hardness, thickness, friability, drug content, weight variation, floating lag time, floating time, mucoadhesive strength, and in vitro drug release. Tablets thus formulated (Batch M-3) provided sustained release using floating and mucoadhesion approaches over a period of 12 h. The project is open for in vivo studies. Conclusions: Metformin HCl (250 mg) table as drug resin complex in mucoadhesive floating matrix can provide advantage for early cases of diabetics. Floating mucoadhesive tablet having metformin HCl complexed with indion 244 is not available in the market and not yet reported in research paper as per literature survey. This could be one of the attempts to increase the oral bioavailability of metformin HCl.

Bioavailability Study of Sustain Release Preparations of Three Widely used NSAIDS Available in Bangladesh

This research has been designed to assess the in vitro bioavailability study of widely distributed and commonly used three analgesic and anti-pyretic drugs namely Diclofenac Sodium, Paracetamol and Ibuprofen sustained release tablets. Three brands of Diclofenac Sodium, four brands of Paracetamol and three brands of Ibuprofen tablets were obtained. Three brands of Diclofenac SR tablets, all brands maintained a steady state release pattern throughout the defined period, i.e. 12 hours. In 1st hour sample D01, D02, D03 were released 43.6%, 36.16%, and 59.85% of drug in dissolution respectively. Four brands of Paracetamol SR tablets, all brands maintained a steady state release pattern throughout the defined period, i.e. 12 hours. In 1st hour sample P01, P02, P03 and P04 were released 78.60%, 89.36%, 74.21%, 78.14 of drug in phosphate buffer (pH 6.8) respectively. Another sustained release tablets was Ibuprofen; all brands maintained a steady state release pattern trough out the defined period, i.e. 12 hours. In 1st hour sample I01, I02, I03 were released 60.46%, 54.02%, 50.57% of drug in phosphate buffer (pH 6.8) respectively. The release rates of the samples were determined for around 12th hours.

Formulation and in vitro, in vivo evaluation of effervescent floating sustained-release imatinib mesylate tablet.

IntroductionImatinib 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.MethodologyFloating 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 DiscussionStatistical 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 Cmax and higher Tmax compared to the conventional tablet (Gleevec). Thus, formulated SR tablets preserved persistent concentration of plasma up to 24 hours.ConclusionIn 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.

Formulation Development and Evaluation of Gabapentin Controlled Release Tablets

The objective of the present study was to develop a pharmaceutically equivalent, stable, robust, cost effective and quality improved formulation of Gabapentin controlled release tablets by using different grades of controlled release polymer. The design of dosage form was performed by choosing Hydroxypropyl Methyl Cellulose (HPMC K100MCR), Hydroxypropyl Methyl Cellulose (HPMC K15MCR), Microcrystalline Cellulose (MCC) and Di-calcium phosphate polymers as matrix builders. The drug-polymer compatibility studies were performed. Blend Uniformity was studied and accordingly the flowability was optimized for the powder blend. Tablets were prepared by direct compression with free flowing powder. The network formed by HPMC, MCC and DCP had been coupled satisfactorily with the controlled resistance, in vitro release and FT-IR. Mean dissolution time was also reported to compare various dissolution profiles. The formula was finalized by comparing the in vitro dissolution with that of the innovator SR and IR tablets. Optimized formulation of Gabapentin was formulated using 23% HPMC K100MCR and 10% of DCP. In vitro drug release profile was examined 98.69% within 12h. The releases of the formulation were fitting to Hixson Crowell model suggesting controlled zero order release from the formulation. The results suggested that direct compression is a suitable method to formulate controlled release Gabapentin tablets and it can perform therapeutically better than conventional immediate release dosage form.

In vitro-in vivo-in silico approach in biopharmaceutical characterization of ibuprofen IR and SR tablets

Within the last decades, physiologically based pharmacokinetic models have emerged into a biopharmaceutical toolkit that has been proven useful in understanding how physicochemical, formulation and physiological factors affect oral drug absorption. The purpose of this study was to develop a drug specific physiologically based pharmacokinetic model that will allow mechanistic interpretation of oral absorption from dosage forms exhibiting different in vitro and different in vivo performance (i.e. immediate release and sustained release tablets) and identification of bioperformance dissolution testing. Ibuprofen was chosen to be used for the “proof of concept” considering it is well characterised and the necessary physicochemical, biopharmaceutical and pharmacokinetic properties for model development could be found in the literature. Gastrointestinal simulation technology implemented in Simcyp® was successful in estimating ibuprofen oral absorption. The developed model exhibited good generalisation ability for the dosage forms studied. The obtained results indicate that the model was sensitive to input kinetics represented by the in vitro drug release profiles obtained under various dissolution conditions. According to the obtained results, reciprocating cylinder apparatus with biorepresentative change in media pH might be considered as bioperformance dissolution in the case of the two ibuprofen SR products studied. These results further justify the use of integrated in vitro-in vivo-in silico approach in estimating bioperformance of oral solid dosage forms.

Pharmaceutical evaluation of effects of hydrophilicity and hydrophobicity of three commonly used diluents on tablet formulation-Part II: SR tablets

The study deals with the effects of hydrophilicity and hydrophobicity of three commonly used diluents on IR tablets of model soluble and insoluble drugs. Conventional tablets with diluents, used individually and in combinations, were prepared by direct compression, dry granulation and wet granulation. Effects of binder amount, disintegrant and its time of addition were evaluated. Tensile strength, friability, disintegration, contact angle, wettability and dissolution of tablets were assessed. Results reveal that hydrophilicity and hydrophobicity of drug and diluents markedly influence various tablet properties and should be thoroughly considered prior formulations.

Formulation and evaluation of sustained release venlafaxine tablets using hydrophilic-hydrophobic polymer combinations by melt granulation

The current research aims to formulate Venlafaxine Sustained Release (VHL-SR) tablets using hydrophilic-hydrophobic polymers combination blends by melt granulation technique which highlights the novelty. The polymers selected for the present study have matrix forming properties. Results of FTIR studies have shown that there were no interactions between the polymers used and the drug VHL. Various formulations of VHL- SR tablets (F1-F16) using different combinations of hydrophilic and hydrophobic polymers viz. Carbopol 71G, HPMC K15M, PEO, sodium CMC, Eudragit RS100 and precirol were formulated. Prior preformulation studies carried out on powder blend showed good flow properties. Routine quality evaluations of the VHL-SR tablets showed the diameter of the tablets of all formulations were found to be 9.0±0.0 mm and thickness ranged between 2.08±0.08 to 2.25±0.14 mm, hardness 4.08±0.20 - 5.50±0.31 kg/cm2 , percentage friability 0.24±0.03 - 0.45±0.01%, weight variation from 0-1.15%, drug content uniformity from 98.17±0.68 to 101.89±0.73%, all within Pharmacoepial limits. Results of in-vitro drug release study indicated that the formulation containing Carbopol 71G (50 mg), Xanthan gum (75 mg) and MCC (50 mg) extended the release of the VHL. Formulation F15 was the optimized one which gave satisfactory release (95.2%) for 16 hr and with a similarity factor (f2) 68.46, the release kinetics best explained by the Korsmeyer-peppas and Higuchi diffusion models. The “N” values between 0.5-1.0 in all the formulations exhibiting a non-Fickian release behavior controlled by a combination of diffusion and chain relaxation mechanism. The formulation showed appreciable stability under accelerated conditions after 2 m.

Suicidal overdose with relapsing clomipramine concentrations due to a large gastric pharmacobezoar

The paper presents a case of fatal intoxication after massive sustained-release clomipramine overdosage with prolonged toxicity related to a large gastric pharmacobezoar. 42-year-old female was admitted to the toxicology unit 14h after drugs ingestion. At admission patient was deeply unconscious, required controlled mechanical ventilation. Serum total level of TCAs was 1955ng/mL. Gastric lavage revealed no pills. Within the next 12h the patient's clinical condition improved. TCAs level decreased to 999ng/mL. However, after another 10h the clinical condition started deteriorating again and the patient went into a deep coma requiring controlled mechanical ventilation. TCAs level increased to 2011ng/mL. X-ray and computed tomography revealed large pharmacobezoar consisted from radio-opaque pills. In the 28thh of hospitalization gastrotomy was performed, confirming presence of pharmacobezoar formed from Anafranil SR tablets. After surgery TCAs level was gradually decreasing. However, the patient's condition did not improve, she died 32h after gastrotomy. Post-mortem analyses revealed drug and its metabolite toxic levels in blood (clomipramine – 1729ng/mL, norclomipramine – 431ng/mL) and toxic levels in internal organs: myocardium (clomipramine – 14,420ng/g, norclomipramine – 35,930ng/g), vitreous humor (clomipramine – 1000ng/mL, norclomipramine – 3110ng/mL).Described case report indicates that sustained release clomipramine tablets may form pharmacobezoar. X-ray and computed tomography examinations should be considered in cases of massive abuse of sustained release clomipramine, particularly if symptoms of intoxication are recurrent or persistent.

Pharmacokinetics of Treprostinil Diolamine in Subjects With End-Stage Renal Disease On or Off Dialysis

Treprostinil diolamine sustained release (UT-15C SR) is being evaluated as an oral therapy for pulmonary arterial hypertension. This study evaluated the pharmacokinetics (PKs) of treprostinil following administration of UT-15C SR in subjects with end-stage renal disease (ESRD) compared with healthy subjects with normal renal function (NRF) and the effect of hemodialysis on the PK parameters of treprostinil. Eight ESRD subjects (requiring dialysis, mean creatinine clearance = 11.5 mL/min) received 2 single doses of 1 mg of UT-15C SR (separated by 2 weeks), with the first dose given immediately after dialysis and the second given 4 hours before the start of dialysis. Eight NRF subjects received a single dose of 1 mg of UT-15C SR. The median Cmax, AUC0-inf, and t1/2 of treprostinil were 680 pg/mL, 3240 hours pg/mL, and 2.35 hours, respectively, in ESRD subjects dosed after dialysis and were 551 pg/mL, 3152 hours pg/mL, and 2.05 hours, respectively, in ESRD subjects dosed before dialysis. In comparison, corresponding values were 730 pg/mL, 3726 hours pg/mL, and 3.54 hours, respectively, in NRF subjects. UT-15C SR of 1 mg was well tolerated by NRF and ESRD subjects. The most frequent adverse event was headache and nausea. There was no substantial difference in treprostinil PKs between ESRD and NRF subjects following administration of UT-15C SR tablets. Hemodialysis did not have clinically important effect on treprostinil PK in ESRD subjects.

Comparative release profile of sustained release matrix tablets of verapamil HCl

Introduction:Verapamil hydrochloride (VH) is a calcium channel blocking agent used in the treatment of hypertension, cardiac arrhythmia and angina pectoris. The short half-life and high frequency of administration of VH makes it a suitable candidate for designing sustained drug delivery system. The aim of the present investigation was to develop a sustained release matrix tablet of verapamil hydrochloride (VH) using ethyl cellulose, methyl cellulose, Eudragit RS 100, hydroxypropyl methylcellulose and carboxymethyl cellulose and to evaluate the drug release kinetics.Materials and Methods:In order to achieve the required sustained release profile, the tablets were prepared by a wet granulation method using avicel PH 101 and magnesium stearate as binder and lubricant, respectively.Results:The formulated tablets were characterized for pre-compression and post-compression parameters and they were in the acceptable limits. The drug release data obtained after an in vitro dissolution study was fitted to various release kinetic models in order to evaluate the release mechanism and kinetics. The criterion for selecting the best fit model was linearity (coefficient of correlation). Drug release mechanism was found to follow a complex mixture of diffusion, swelling and erosion. Furthermore, to minimize the initial burst drug release, batches were coated by using Eudragit RS100 polymer. After coating the tablets, a better release profile of the formulated tablets was expected and the release rate of the drug was compared with the marketed SR tablet of VH.Conclusion:The dosage form holds the potential to control the release rate of drug and extend the duration of action of a drug.

Formulation and Comparative Bioavailability of 2 Ciprofloxacin Sustained Release Tablets

The aim of this study is to formulate and evaluate the quality of ciprofloxacin (CAS number: 85721-33-1) sustained release tablet (Ciprocare®XR) 1 000 mg ciprofloxacin (test formulation) by comparing its pharmacokinetic parameters with Cipro®XR sustained release tablet (reference formulation). For this purpose ciprofloxacin SR tablets were developed using the 2-layer method. To assess the quality of the produced sustained release tablets a randomized, 2-way, crossover, bioequivalence study was performed in 24 healthy, male volunteers. The selected Middle Eastern volunteers were divided into 2 groups of 12 subjects. One group was treated with the reference formulation and the other one with the test formulation, with a cross-over after a drug washout period of 7 days. Blood samples were collected at fixed time intervals and Ciprofloxacin concentrations were determined by a validated HPLC assay method. The pharmacokinetic parameters AUC0-48, AUC0-∞, Cmax, Tmax, Ke and T1/2 were determined for both sustained release tablets and were compared statistically to evaluate the bioequivalence between the 2 formulations of ciprofloxacin, using the statistical model recommended by the FDA. The analysis of variance (ANOVA) did not show any significant difference between the 2 formulations and 90% confidence intervals (CI) fell within the acceptable range for bioequivalence. According to the obtained results it was concluded that the test and reference formulations are bioequivalent, since they exhibit comparable pharmacokinetic parameters.

Development of sustained release antipsychotic tablets using novel polysaccharide isolated from Delonix regia seeds and its pharmacokinetic studies

A natural polysaccharide was isolated from the seeds of Delonix regia. The isolated polysaccharide could maintain aqueous equilibrium between the dosage form and the surrounding medium due to its massive competence of water absorption (80.72%) and swelling index (266.7%). The Scanning Electron Micrograph of a polysaccharide exhibits rough surface with pores and crevices, hence, the drug release will be retarded because of the drug particles entrapment in the pores and crevices. Further, the surface tension of polysaccharide is higher than that of water, which may facilitate sustained release of drugs from dosage forms. An antipsychotic drug, quetiapine fumarate has a short half-life of 6h and administered multiple times per day. Hence the quetiapine fumarate oral sustained release tablets were formulated using this polysaccharide in the concentration of 5–30% to avoid the side effects and increase patient compliance. Dissolution of the developed tablets with 25% polysaccharide content showed a better release profile than the other batches (5–20%) at the end of 12h. The strong matrix complex has low solubility in water, it does not dissolve rapidly and the drug continues to diffuse through the gel layer at a consistent rate. Drug release from the matrix tablets follows matrix type except F-4 and F-5 which follow first order and Hix.crow type. The bioavailability study was carried out using healthy male New Zealand white rabbits that show the AUC(0–inf) value for developed SR tablets is 1.44 times higher than the reference thus, indicating more efficient and sustained drug delivery capable of maintaining plasma drug levels better.

Effect of Kollidon® SR on the release of Albuterol Sulphate from matrix tablets

The objective of this study was to evaluate Kollidon SR for the development of extended release Albuterol Sulphate matrix tablets in comparison with other polymers as Hydroxypropylmethylcellulose K15M, Carbopol 71G NF, and Eudragit L100-55. The mechanical properties of the tablets were improved as concentration of Kollidon SR or other polymers increased. It was found that Kollidon SR 30% (w/w) and HPMC 30% (w/w) tablets have f 2 similarity factor of 83.5 in their Albuterol Sulphate dissolution profile. The marketed product was found to release 99.7% of drug content within 8 h, while Kollidon SR and HPMC tablets with 30% (w/w) polymer concentration level released 92.7% and 92.9% respectively of drug content within 8 h. Kollidon SR has a unique character of maintaining tablets geometric shape until the end of dissolution test, this is mainly due to the water insoluble content, polyvinyl acetate, forming 80% (w/w) of Kollidon SR, while the remaining content 20% (w/w) is the water soluble, polyvinylpyrrolidone, responsible for pore formation causing a diffusion controlled release. Drug release from all previous formulations is best described to be controlled by more than one kinetic mechanism of release. In conclusion, Kollidon SR and HPMC and Carbopol were found to be potential candidates for the development of extended release of Albuterol Sulphate tablets.

Development and Optimization of a Novel Sustained-release Tablet Formulation for Bupropion Hydrochloride using Box-Behnken Design

【The objectives of this study were to evaluate the effect of formulation ingredients on the drug release and to optimize the novel sustained release matrix tablet formulations of bupropion hydrochloride. A three factor, three-level Box-Behnken design was used for the optimization procedure, with the amounts of PEO ( $X_1$ ), citric acid ( $X_2$ ) and Compritol 888 ATO ( $X_3$ ) as the independent variables. The selected dependent variables were the cumulative percentage values of bupropion hydrochloride that had dissolved after 1, 4 and 8 hr. Various dissolution profiles of the drug from sustained release matrix tablets were obtained. Optimization was performed for $X_1$ , $X_2$ and $X_3$ using the following target ranges; $30%{\leq}Y_1{\leq}45%$ ; $70{\leq}Y_2{\leq}85%$ ; $85%{\leq}Y_3{\leq}100%$ . The optimized formulation for bupropion hydrochloride was achieved with 12.5% PEO ( $X_1$ ), 2.5% citric acid ( $X_2$ ) and 10% Compritol 888 ATO ( $X_3$ ). The sustained release matrix tablets with the optimized formulation provided a release profile that was close to predicted values. In addition, the dissolution profiles of the sustained release matrix tablet with the optimized formulation were similar to those of the commercial product Wellbutrin $^{(R)}$ SR tablets ( $f_2$ =79.8 79.83).】

In vitro and in vivo evaluation of hydrophilic and hydrophobic polymers-based nicorandil-loaded peroral tablet compared with its once-daily commercial sustained-release tablet

Context: Hydrophilic and hydrophobic polymer-based nicorandil (10 mg)-loaded peroral tablets were prepared using the wet granulation technique. The influence of varying amounts of hydroxypropyl methylcellulose (HPMC) (30–50 mg), ethylcellulose (2–4 mg), microcrystalline cellulose (5–20 mg) and Aerosil® (5–12 mg) in conjunction with the constant amounts (3 mg) of glidant and lubricant (magnesium stearate and talc) on the in vitro performances of the tablets (hardness, friability, weight variation, thickness uniformity, drug content, and drug release behavior) were investigated. Objective: The objectives of this study were (i) to select a nicorandil-loaded peroral tablet that matched the in vitro dissolution profile of once-daily commercial sustained-release tablet, and (ii) to compare the in vivo sustaining/controlling efficacy of the selected peroral tablet with that of its commercial counterparts. Results and Discussion: Because the nicorandil (10 mg)-loaded tablet prepared based on F-IX composition (50 mg HPMC, 4 mg ethylcellulose, 10 mg MCC and 3 mg glidant and lubricant) showed a release profile comparable to that of the Nikoran® OD SR tablet release profile, the tablet with this composition was considered to be the optimized/selected formulation and, therefore, was subjected to stability study and in vivo study in rabbits. Despite of the higher Cmax and AUC values obtained with the optimized tablet, there was no sign of difference between the optimized- and Nikoran® OD SR- tablets following a single-dose crossover oral administration into rabbit. Conclusion: The optimized tablet could be used as an alternative to the commercial once-daily tablet.