Pulsatile Release Tablets Research Articles

Formulation, Optimization, and Evaluation of Ezetimibe for Chronotherapeutic Drug Delivery using Compression-Coating Technology

Objectives: The purpose of the present study was to Formulation, optimization and evaluation of drug for chronotherapeutic drug delivery using compression coating technology for hypercholesterolemia. Material and Methods: The drug delivery system was designed to deliver the drug at a time when it could be needed for the most in the early morning (4 to 6 a.m.) for patients in case of hypercholesterolemia. The pulsatile concept was applied to the dosage form by having a lag phase followed by an immediate release. The prepared system consisted of two parts: a core tablet containing the active ingredient and fracture outer shell with delay-release polymer having diffusion characteristics. Solid dispersion was carried out by screening of betacyclodextrin, Polyvinyl pyrrolidone (PVP K30), and HPMC using three different drug complex ratios 1:1, 1:2, and 1:3 by a solvent evaporation method through spray dryer. The immediate-release core tablet (IRCT) was prepared by using a superdisintegrant with active ingredients. Screening of IRCT was carried out by pre and post compression parameters, disintegration time and an in-vitro dissolution study. The pulsatile release tablet (PRT) of optimized IRCT was made by Glyceryl Behenate and Dibasic Calcium Phosphate. Optimization of polymer concentration of PRT was carried out by pre and post-compression parameters, pulsatile lag time, and an in-vitro dissolution study. A 32 factorial design was employed to optimize the PRT. The design consisted of two dependent variables R1, and R2 independent variables X1 and X2. The two independent formulation variables selected for the study including Concentration of coating polymer and Concentration of lubricant. The dependent variables are Lag Time and Thickness. Results: XRD, DSC and FTIR spectra showed that solid dispersion was formed by the drug and PVP K30 complex. IRCT batch RR1 containing 22mg croscarmellose sodium to achieve good 30sec disintegration time and 98.34% drug release at the end of 20 minutes of Ezetimibe respectively. PRT formulation DR6 showed good pre and post-compression parameters with a satisfactory drug release of 98.34% for Ezetimibe respectively with a lag time of 6 hours. The 32 factorial design was used for the optimization of PRT parameters. A total of 9 experiments were performed for two factors at three levels each. The optimized batch showed 98.27% DR for Ezetimibe in 6.2 hrs (within 20 min after lag time) with pulsatile lag time up to 6.0 hrs and thickness of 5.10 kp. Conclusion: It was concluded that tablet within the tablet, pulsatile drug delivery of Ezetimibe (BCS class-II drugs) was successfully formulated with the advantage of enhanced solubility, and pulsatile release behavior and had an added benefit of suitable for chronopharmacotherapy of diseases that show circadian rhythms in their pathophysiology.

Press coated Bioadhesive Pulsatile Tablet of Lisinopril for Chronotherapy of Cardiac Disorders: in-vitro Evaluation

The purpose of present investigation was to formulate bioadhesive pulsatile release tablet (BPRT) of lisinopril drug belong to antihypertensive category for chronotherapy of cardiac disorder. The concept behind this dosage form development is to investigate effect of coating polymer concentration on lag time and drug release from directly compressed tablet. The core tablets prepared by using various concentrations of disintegrants found suitable for complete release of drug in acidic medium indicating its solubility in gastric fluid. The FT-IR studies indicate that selected polymers are compatible with lisinopril since no interaction found in drug-excipient compatibility studies. The dissolution study clearly indicates that higher concentration of polymers which is HPMC K100M and Carbopol reduces free water volume and increase viscosity of the tablet coat causes reduction in drug release. The prepared Bioadhesive pulsatile release tablets showed desired hardness and good mucoadhesion strength. The obtained results showed capability of formulated bioadhesive pulsatile drug delivery system in a drug release for a programmable period of time to attain drug release after minimum 3 hr of Lag time. A stability results clearly indicate that developed pulsatile product was sufficiently stable under accelerated and controlled conditions. Thus, the developed pulsatile tablet can be considered to be a promising formulation for the relief of early morning surge in blood pressure and other cardiac disorders which follows a circadian rhythm.

Formulation and Evaluation of Pulsatile Drug Delivery System of Atenolol

The objective of the present study was formulation and evaluation of pulsatile release tablets of Atenolol. A tablet system consisting of cores which was coated with layers of swelling and rupturable coatings. Cores containing Atenolol as model drug were prepared by direct compression with appropriate ratios of lactose and microcrystalline cellulose and then coated sequentially with different ratios of an inner swelling layer containing HPMC and an outer rupturable layer of Ethyl Cellulose. The effect of level of swelling layer and rupturable coating was investigated. The different formulation press coated by using different weight ratios of Hydroxy Propyl Methyl Cellulose (HPMC) / Ethyl Cellulose (EC) / both HPMC and EC. The optimum result was achieved in formulation containing HPMC: EC weight ratios. The F3 batch achieved a highest burst release after the lag time which is applicable pulsatile drug delivery system of Atenolol.

FORMULATION DEVELOPMENT AND EVALUATION OF CHRONOMODULATED DRUG DELIVERY SYSTEM BY ZAFIRLUKAST

Objective: The main objective of the present study was to formulate and evaluate a time-controlled single-unit oral pulsatile drug delivery system containing Zafirlukast for the prevention of nocturnal asthma attacks. To provide time-scheduled drug release for Asthma disease. It is used for preventing asthmatic attacks at early morning. Pulsatile release dosage form is increasing patient compliance by reducing the dosing frequency, especially in the early morning.
 Methods: Core tablets were prepared by incorporating different concentrations of natural and synthetic super disintegrants. Drug-containing core tablets (ZC1-ZC15) with different compositions of natural super disintegrants (Plantago ovata seed powder, Locust bean gum) synthetic super disintegrants (Sodium starch glycolate (SSG), Cross carmellose sodium (CCS), Crospovidone (CP)) were prepared by direct compression technique. The core tablets were subjected to pre-formulation, physicochemical and In vitro drug release studies. The fast disintegrating core tablet formulation was selected and press-coated tablets (P1-P11) were prepared with different compositions of hydrophobic polymers Eudragit RS100, Eudragit RL 100, Ethylcellulose and hydrophilic polymers Hydroxypropyl methylcellulose K4M, K100M. The optimized formulation was selected and quantified based on in vitro drug release profile in simulated gastric and intestinal fluids.
 Results: The pre and post-compression parameters of tablets were also found to be within limits. Formulation ZC5 with 16 mg of Locust bean gum showed the least disintegrating time, i.e., 22.13 sec, and was selected as the best immediate release core tablet. The press-coated tablet formulation P8 having 62.5 mg Eudragit RS100 and 62.5 mg of HPMC K4M in ratio 1:1 over the core tablet ZC5 showed rapid and drug release nearly after 4 h lag time and 98.86 % up to 12 h. Accelerated stability studies of the optimized formulation P8 indicated no significant difference in release profile after 3 mo.
 Conclusion: The in vitro dissolution study showed that lag time before drug release was highly affected by the coating amount level and nature of coating polymer used. Time-controlled pulsatile release tablets can be prepared using press-coating techniques.

Physicochemical Characterization of Bi-Layered Terbutaline Sulfate Tablets for Chronotherapeutic Pulsatile Drug Delivery Design Based on Natural and Synthetic Polymer using Direct Compression Technique

The aim of the strategy to formulate the pulsatile drug delivery system using terbutaline sulfate by direct compression technique and evaluate the effects of formulation and dissolution medium on the behavior of drug release, and to clarify the drug release mechanism based on acquiring results. Pulsatile release tablets include a drug and disintegrating agent-containing core and swellable external layers for slow down drug release, then rupturing the nearby surrounding outer layer for fast release. Core tablets prepared using disintegrating agent by direct compression method and coated with polymers like HPMC K100M, ethyl cellulose, karaya gum in different quantities. Several physical parameters of the tablets evaluated such as stiffness, thickness, friability, weight variation, disintegration, drug content and dissolution test. Terbutaline sulfate released from bi-layered tablets with pulsatile behaviors. In-vitro drug release rate readings showed that F3 and F6 are best based on the less quantity of drug release during the lag time (11% and 14% in 5 h). So, from the result, the F6 has nominated the best formulation. Thus, by the direct compression method prepared, coated tablets before drug release with an obvious lag time is possibly useful preparation for the medication of osteoarthritis, rheumatoid arthritis, dysmenorrhea, asthma which follows a circadian rhythm. It confirmed that eroding, diffusion, and swelling mechanisms were responsible for drug release. Ultimate pulsatile release activities may be done by modifying polymeric membrane quantities and proportions to meet the condition of pulsatile activities.

Trimetazidine Dihydrochloride Pulsatile-Release Tablets for the Treatment of Morning Anginal Symptoms: Dual Optimization, Characterization and Pharmacokinetic Evaluation.

This research work aimed to target the early morning peak symptoms of chronic stable angina through formulating antianginal drug, Trimetazidine (TMZ) in a pulsatile-release tablet. The core formulae were optimized using 22 .31 factorial design to minimize disintegration time (DT) and maximize drug release after 5 minutes (Q5min). Different ratios of Eudragit S100 and Eudragit L100 were used as a coating mixture for the selected core with or without a second coating layer of hydroxypropyl methylcellulose (HPMC E50). The different formulation variables were statistically optimized for their effect on lag time and drug release after 7 hours (Q7h) using BoxBehnken design. The optimized formula (PO) was subjected to stability study and pharmacokinetic assessment on New Zealand rabbits. The optimal core (F8) was found to have 1.76 min disintegration time and 61.45% Q5min PO showed a lag time of 6.17 h with 94.80% Q7h and retained good stability over three months. The pharmacokinetics study confirmed the pulsatile-release pattern with Cmax of 206.19 ng/ml at 5.33 h (Tmax) and 95.85% relative bioavailability compared to TMZ solution. Overall pulsatile-release tablets of TMZ successfully released the drug after a desirable lag time, providing a promising approach for early morning anginal symptoms relief.

Preparation and Drug Release Mechanism of Time Controlled Explosive Pulsatile Tablets with Ethylcellulose Coating

Core tip: The development of pharmacology in the decade revealed the biological rhythm of the occurrence and development of certain diseases, usually the circadian rhythm. Therefore, chronopharmacological drug delivery is of great significance in the prevention and treatment of diseases having onset rhythm inconvenient to take drug. An easy-to-prepared, time-controlled explosive metoprolol tartaric pulsatile tablet was developed in order to provide patients with timed therapy of effective blood drug concentration at the optimal time. The formulation and process were optimized using single factor experiments and orthogonal experiments. In addition, the swelling and water absorption rate of tablet and the mechanical properties of the coating film were measured to further reveal its release mechanism. The results showed that the strong tensile strength of coating film and the weak flexibility of EC film resulted in a shell-type exploding rupture of the coating film followed by the pulsatile fast release of drug when the swelling force of core tablet caused by water uptake was high enough. Both the swelling capacity of core tablets and the thickness of coating film together controlled the lag time of drug release. The prepared time-controlled explosive pulsatile tablets with ethylcellulose coating thereafter are expected to be used for the delivery of therapeutic agents for chronotherapy by adjusting the lag time of drug release to match the different high attack rhythm of the exact diseases. Abstract: Background The time rhythm of human body is associated with the occurrence and development of many diseases, and it also affects the efficacy and pharmacokinetic characteristics of the corresponding therapeutic drugs. Therefore, the chronopharmacological drug delivery system has potential applications. Aim In this work, it is proposed to develop a kind of pulsatile release tablet of simple structure and preparing process, thus to provide an alternative drug delivery system for therapeutic agents used in treatment of diseases of typical onset biorhythm at period inconvenient to take drug. Methods Metoprolol tartrate (MT), a drug widely used clinically to treat cardiovascular diseases was selected as a model drug for developing pulsatile tablets of time-controlled explosive system (TES). The MT pulsatile tablets were ethyl cellulose (EC) coating tablets produced by pan coating process, and the core tablets were prepared by direct compression. The formulation and process was optimized by single factor test and orthogonal design. Also, the pulsatile release mechanism of the tablets was discussed through investigating the water absorption and swelling capacity of tablets as well as the mechanical properties of EC free film. Results A kind of pulsatile tablets of MT were developed with a drug release lag time around 7 h and a fast release of drug after lag time. When the swelling force of core tablet caused by water uptake was high enough over the tensile strength of EC coating film, the MT pulsatile tablets demonstrated a shell-type exploding rupture due to the great rigidity and weak flexibility of EC film, and then a fast pulsatile release of drug was observed. Both the swelling capacity of core tablet and the thickness of coating film together controlled the lag time of drug release. The lag time showed a good linear relationship with the thickness of coating film (r = 0.9984, P < 0.01). The sort and amount of fillers and disintegrants dominated the release behaviour after lag time. Conclusion The developed MT pulsatile tablets can exert a timely release of drug before peak onset period of hypertension and angina pectoris early in the morning after drug taking around 22:00 P.M the night before. The good linear relationship between lag time and coating thickness enabled the pulsatile tablets to be used for delivery of other therapeutic agents of similar chronotherapy demand by adjusting the coating thickness to achieve the appropriate lag time of drug release to match the different high attack rhythm of the exact diseases.

Formulation and in vivo Evaluation of Chronomodulated Drug Delivery of Nimodipine

Chronotherapy has been emerging as a novel technology in the field of pharmaceutical research. Delivery of drugs with respect to the circadian rhythm has gained greater importance in the diseases such as diabetes, asthma and hypertension in producing maximum therapeutic action. Present study focus on the formulation and evaluation of Nimodipine pulsatile release tablets with the incorporation of Eudragit pH sensitive polymers used for the chronotherapy of hypertension. Pharmacologically Nimodipine is an anti-hypertensive agent that acts by blocking the L and N-type calcium channels. Evaluation parameters for Nimodipine tablets included friability, drug content, bulk and tapped density, angle of repose and Carr’s index and drug release in vitro and in vivo.

3D Printing in Personalized Drug Delivery.

Personalized medicines are becoming more popular as they enable the use of patient's genomics and hence help in better drug design with fewer side effects. In fact, several doses can be combined into one dosage form which suits the patient's demography. 3 Dimensional (3D) printing technology for personalized medicine is a modern day treatment method based on genomics of patient. 3D printing technology uses digitally controlled devices for formulating API and excipients in a layer by layer pattern for developing a suitable personalized drug delivery system as per the need of patient. It includes various techniques like inkjet printing, fused deposition modelling which can further be classified into continuous inkjet system and drop on demand. In order to formulate such dosage forms, scientists have used various polymers to enhance their acceptance as well as therapeutic efficacy. Polymers like polyvinyl alcohol, poly (lactic acid) (PLA), poly (caprolactone) (PCL) etc can be used during manufacturing. Varying number of dosage forms can be produced using 3D printing technology including immediate release tablets, pulsatile release tablets, and transdermal dosage forms etc. The 3D printing technology can be explored successfully to develop personalized medicines which could play a vital role in the treatment of lifethreatening diseases. Particularly, for patients taking multiple medicines, 3D printing method could be explored to design a single dosage in which various drugs can be incorporated. Further 3D printing based personalized drug delivery system could also be investigated in chemotherapy of cancer patients with the added advantage of the reduction in adverse effects. In this article, we have reviewed 3D printing technology and its uses in personalized medicine. Further, we also discussed the different techniques and materials used in drug delivery based on 3D printing along with various applications of the technology.

FORMULATION AND EVALUATION OF PULSATILE DRUG DELIVERY SYSTEM OF SALBUTAMOL SULFATE FOR THE CHRONOTHERAPY OF ASTHMA

Objective: The main objective of the present study was to design and evaluate a time-controlled single unit oral pulsatile drug delivery system containing salbutamol sulfate for the prevention of nocturnal asthma attacks.Methods: Drug containing core tablets (C1-C10) with different composition of superdisintegrants such as sodium starch glycolate, croscarmellose sodium, and crospovidone were prepared by direct compression technique. The fast disintegrating core tablet formulation was selected, and press-coated tablets (P1-P11) were prepared with different compositions of hydrophobic and hydrophilic polymers: Ethylcellulose-20 (EC-20), hydroxypropyl methylcellulose K4M, and low substituted hydroxypropyl cellulose (L-HPC LH11). The coating polymers were selected and quantified based on in vitro lag time and drug release profile in simulated gastric and intestinal fluids.Results: Formulation C10 with 7.5% crospovidone showed least disintegrating time, i.e., 0.31 min and was selected as the best immediate release core tablet. The press-coated tablet formulation P11 having 360 mg barrier layer of EC-20 and L-HPC LH11 in ratio 14:1 over the core tablet C10 showed rapid and complete drug release nearly after 6 h lag time. Accelerated stability studies of the optimized formulation P11 indicated no significant difference in release profile after a period of 6 months.Conclusion: The in vitro dissolution study showed that lag time before drug release was highly affected by the coating level and nature of coating polymer used. Time-controlled pulsatile release tablets can be prepared using press-coating techniques.

DESIGN AND EVALUATION OF CHRONOTHERAPEUTIC PULSATILE DRUG DELIVERY SYSTEM OF CILNIDIPINE

Objectives: Cilnidipine is the novel calcium antagonist accompanied with L-type and N-type calcium channel blocking function used for the treatment of hypertension. The aim of present work is formulate and evaluate a press coated pulsatile release tablets of Cilnidipine using an admixture of hydrophilic polymers in order to achieve a predetermined lag time for chronopharmacotherapy of Hypertension. Methods: The pulsatile drug release tablets were prepared by compression coating method. The tablets prepared were evaluated for different properties like bulk density, tapped density, angle of repose and Carr’s index), hardness, thickness, weight variation, friability, drug content uniformity and in vitro drug release study. Results: All formulations have shown good flow properties. The hardness of tablets ranged between 4.93±0.08 to 5.96±0.11 kg/cm2, percentage friability of tablets ranged between 0.68±0.21 to 0.82±0.06. Maximum drug release was found to be 94.39%. Conclusion: Study concludes that the prepared pulsatile drug delivery system can be considered as one of the promising formulation technique for delivery of Cilnidipine. Formulation of batch CPT1was found to be optimum. Peer Review History: Received 15 September 2017; Revised 28 October; Accepted 5 November, Available online 15 November 2017 Academic Editor: Ahmad Najib, Universitas Muslim Indonesia, Indonesia, ahmad.najib@umi.ac.id UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 4.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Dr. Viney Chawla, University Institute of Pharmaceutical Sciences, Baba Farid University of Health Sciences, Sadiq Road, Faridkot-Punjab 151203, drvineychawla@gmail.com Dr. Barkat Ali Khan, Kampala International University , Uganda, barki.gold@gmail.com

Design, Development and Optimization of Pulsatile Core in Cup Tablets of Naproxen

The aim of the present study to prepare Pulsatile release tablet of naproxen for the treatment of rheumatoid arthritis. The drug delivery system was designed to deliver the drug at a time when it could be most needful for the patient. Drug excipient compatibility studies were carried out using DSC and found to be compatible with each other. Pulsatile tablet was prepared by direct compression method using different type and amount of superdisintegrants and coating polymers and evaluated for pre and post compression parameters. Box Behnken design was applied to optimize responses. Concentrations of Sodium starch glycolate (SSG) (X1), Ethyl cellulose (EC) (X2), and HPMC K100M (X3) were selected as independent variables while Lag time (Y1) and % drug release at 8 hrs (Y2) were selected as dependent variables. The prepared tablets were evaluated for post compression parameters and results indicated that concentration of SSG has major effect on in vitro drug release while concentration of EC and HPMC K100M has major effect on Lag time. Batch BE13 prepared with SSG 35mg, EC 175mg, and HPMC K100M 75 mg was found to be best batch as it achieves predetermined lag time of 5 hr 02 min and 99.32% of drug release. There was no significant variation in formulation at the end of six month accelerated stability study.

A Three-Pulse Release Tablet for Amoxicillin: Preparation, Pharmacokinetic Study and Physiologically Based Pharmacokinetic Modeling.

BackgroundAmoxicillin is a commonly used antibiotic which has a short half-life in human. The frequent administration of amoxicillin is often required to keep the plasma drug level in an effective range. The short dosing interval of amoxicillin could also cause some side effects and drug resistance, and impair its therapeutic efficacy and patients’ compliance. Therefore, a three-pulse release tablet of amoxicillin is desired to generate sustained release in vivo, and thus to avoid the above mentioned disadvantages.MethodsThe pulsatile release tablet consists of three pulsatile components: one immediate-release granule and two delayed release pellets, all containing amoxicillin. The preparation of a pulsatile release tablet of amoxicillin mainly includes wet granulation craft, extrusion/spheronization craft, pellet coating craft, mixing craft, tablet compression craft and film coating craft. Box–Behnken design, Scanning Electron Microscope and in vitro drug release test were used to help the optimization of formulations. A crossover pharmacokinetic study was performed to compare the pharmacokinetic profile of our in-house pulsatile tablet with that of commercial immediate release tablet. The pharmacokinetic profile of this pulse formulation was simulated by physiologically based pharmacokinetic (PBPK) model with the help of Simcyp®.Results and DiscussionSingle factor experiments identify four important factors of the formulation, namely, coating weight of Eudragit L30 D-55 (X1), coating weight of AQOAT AS-HF (X2), the extrusion screen aperture (X3) and compression forces (X4). The interrelations of the four factors were uncovered by a Box–Behnken design to help to determine the optimal formulation. The immediate-release granule, two delayed release pellets, together with other excipients, namely, Avicel PH 102, colloidal silicon dioxide, polyplasdone and magnesium stearate were mixed, and compressed into tablets, which was subsequently coated with Opadry® film to produce pulsatile tablet of amoxicillin. In vitro release study firstly indicated a three-pulse release profile of the tablet. Later the pulse tablet was found to generate the sustained release of amoxicillin in beagle dogs. Furthermore, the Simcyp® software was used to simulate the in vivo concentration time curve model of the three-pulse release tablet for amoxicillin in both human and beagle dog. The prediction by PBPK model nicely fitted the observation in human and beagle dog.ConclusionsThis study has demonstrated the interrelation of factors affecting the pulsatile formulation of amoxicillin using a Box–Behnken design. The three-pulse release tablets of amoxicillin were proven to generate pulsatile release in vitro and sustained release in vivo. This formulation was also found to extend the effective plasma concentration in human compared to the tablet of immediate release based on the simulation data by PBPK modeling. This study provides an example of using PBPK to guide the development of pulsatile dosage forms.

Formulation and Evaluation of Floating Pulsatile Drug Delivery System of Ibuprofen and Ranitidine Combination

Since rheumatoid arthritis patients experience severe pain, inflammation, and joint stiffness in the early morning hours a pulsatile drug delivery system of a suitable anti-inflammatory drug that is administered at bedtime but release the drug in the early morning would be a promising system. The objective of this work was to develop a pulsatile release tablet containing a combination of ibuprofen and ranitidine HCl from which ibuprofen gets released after a lag time of 6-7 hours. The methodology involves; analytical method development for simultaneous estimation of combination drugs, development of pulsatile release tablet and an in vivo study in rats. Lag time was controlled by coating the rapid release core tablet with different grades and concentrations of HPMC polymer. A floating gastroretentive layer was applied on top to prevent metabolism of ranitidine at the last part of the intestine. Six different formulations were prepared with three different concentrations of HPMCK4M and HPMCK100M. In vitro studies showed that the lag time increased with an increase in both concentration and viscosity of polymers. The formulation where the core tablet was coated with 100 mg of HPMCK100M had an optimum lag time of 6.3 hrs. In vivo study evaluated the ulcer protection of the formulation in four animal groups; first group remained as control, the second group received ibuprofen at a dose of 180 mg/kg, third and fourth groups received a combination of both the drugs but ranitidine in different doses. Based on this research, it can be concluded that pulsatile release of ibuprofen tablets can be successfully formulated by using HPMC polymers. The usage of ranitidine along with ibuprofen reduces the ulcerogenecity of the later.

Gastroretentive pulsatile release tablets of lercanidipine HCl: development, statistical optimization, and in vitro and in vivo evaluation.

The present study was aimed at the development of gastroretentive floating pulsatile release tablets (FPRTs) of lercanidipine HCl to enhance the bioavailability and treat early morning surge in blood pressure. Immediate release core tablets containing lercanidipine HCl were prepared and optimized core tablets were compression-coated using buoyant layer containing polyethylene oxide (PEO) WSR coagulant, sodium bicarbonate, and directly compressible lactose. FPRTs were evaluated for various in vitro physicochemical parameters, drug-excipient compatibility, buoyancy, swelling, and release studies. The optimized FPRTs were tested in vivo in New Zealand white rabbits for buoyancy and pharmacokinetics. DoE optimization of data revealed FPRTs containing PEO (20% w/w) with coat weight 480 mg were promising systems exhibiting good floating behavior and lag time in drug release. Abdominal X-ray imaging of rabbits after oral administration of the tablets, confirmed the floating behavior and lag time. A quadratic model was suggested for release at 7th and 12th h and a linear model was suggested for release lag time. The FPRT formulation improved pharmacokinetic parameters compared to immediate release tablet formulation in terms of extent of absorption in rabbits. As the formulation showed delay in drug release both in vitro and in vivo, nighttime administration could be beneficial to reduce the cardiovascular complications due to early morning surge in blood pressure.

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

Objective: The intent of the present investigation is to develop colon targeted compression coated flurbiprofen pulsatile release tablets that retard the drug release in the upper gastro intestinal system but progressively release in the colon.Materials and methods: Flurbiprofen core tablets were prepared by direct compression method and were compression coated with hydroxypropyl methylcellulose and Eudragit S100. The formulation is optimized based on the in vitro drug release study and further evaluated by X-ray imaging and pharmacokinetic studies in healthy humans for colonic delivery.Results and discussions: The optimized formulation showed negligible drug release (7.26 ± 0.05%) in the initial lag period followed by progressive release (99.27 ± 0.46%) for 24 h. The X-ray imaging study in human volunteers showed that the tablets reached the colon without disintegrating in the upper gastrointestinal tract. The Cmax of colon targeted tablets was 10792.62 ng/mL at Tmax 10 h where as in case of immediate release tablets the Cmax was 15684.79 ng/mL at Tmax 3 h signifies the ability of compression coated tablets to target the colon.Conclusion: Development of pulsatile release compression coated tablets using combination of time dependent and pH sensitive approaches was suitable to target the flurbiprofen to colon.

Comparison between Ethylcellulose Aqueous Colloidal Dispersion and Ethylcellulose Ethanolic Solution as Rupturable Coating Materials for Pulsatile Release Tablets

Pulsatile release dosage forms which time of drug release can be determined have shown advantages for various drugs such as chronopharmacological drugs and drugs with high first pass metabolism. The pulsatile release tablets consisting of drug-containing cores coated with inner swelling layer containing a superdisintegrant (croscarmellose sodium (Ac-Di-Sol®)) and outer rupturable layer (ethylcellulose (EC)) were previously developed. In this study, two different types of EC coating membrane, EC ethanolic solution (ECS) versus EC aqueous colloidal dispersion (ECD), were compared. Propranolol HCl was used as a model drug. Effect of rupturable coating level on lag time and drug release was investigated. The results demonstrated that using ECS could provide the pulsatile release tablets with obviously longer lag time than ECD. With ECS, increasing of rupturable coating level increased lag time of the pulsatile release tablets because of the lowered water uptake. In addition, rapid drug release after the predetermined lag time was achieved in the pulsatile release tablets using ECS. However, the pulsatile tablets with ECD ruptured within a few minutes even high levels of rupturable coating were used. It was suggested that the different performance of the pulsatile release tablets with different types of EC might be related to the discrepancy in physical properties of the obtained EC membrane.

Design and in vitro evaluation of compression-coated pulsatile release tablets of losartan potassium

In majority of individuals blood pressure rises in the early morning hours, which lead to serious cardiovascular complications. Formulation of pulsatile system makes it possible to deliver drug at definite period of time when symptoms of the disease condition are most critical. The purpose of the present work was to develop pulsatile release tablet of losartan potassium for chronotherapy in hypertension. The prepared system consisted of a core tablet coated with versatile and safe hydrophilic cellulosic ethers such as, hydroxypropyl methylcellulose, hydroxypropyl cellulose and sodium carboxy methylcellulose to produce burst release after predetermined lag time. Various formulation factors were studied through series of test and in vitro dissolution study. It was found that core tablets containing superdisintegrant failed to produce burst drug release pattern while effervescent agent was able to do so. Results also reveal that coating composition and coating level affects lag time. Formulation containing effervescent agent in core and coated with 200 mg hydroxypropyl cellulose provide lag time of 4.5 h with 73% drug release in 6 h that followed a sigmoidal release pattern. These values were close to the desired objective of producing lag time of 5-6 h followed by fast drug release. This approach can thus provide a useful means for timed release of losartan and is helpful for patients with morning surge.

Preparation and in vitro release characteristics of pulsed-release tablets of Apocynum venetum

Using Apocynum venetum as a model drug to prepare pulsed-release tablets based on diffusion, swelling, osmotic pressure mechanism and to evaluate the release characteristics. The pulsatile release tablets were prepared by film coating methods using HPMC E5 and Eudragit The effect of formulation on pulsatile release of A. venetum was investigated. The pulsed-release tablet was prepared by a swelling layer coating which contains HPMC E5 and a controlled-release membrane containning Eudragit. The delayed release time of the tablets was (5.0 +/- 0.5) h. The pulsatile release characteristics of A. venetum pulsatile release tablets were confirmed in vitro.

Rabeprazole extended-release 50 mg compared with esomeprazole 40 mg and rabeprazole delayed release 20 mg

Rabeprazole extended-release 50 mg compared with esomeprazole 40 mg and rabeprazole delayed release 20 mg