Effect of core size and excipients on the lag time and drug release from a pulsatile drug delivery system

Objective: The objective of this research work was to develop and evaluate the floating– pulsatile drug delivery system (FPDDS) of meloxicam intended for Chrono pharmacotherapy of rheumatoid arthritis. Methods: The system consisting of drug containing core, coated with hydrophilic erodible polymer, which is responsible for a lag phase for pulsatile release, top cover buoyant layer was prepared with HPMC K4M and sodium bicarbonate, provides buoyancy to increase retention of the oral dosage form in the stomach. Meloxicam is a COX-2 inhibitor used to treat joint diseases such as osteoarthritis and rheumatoid arthritis. For rheumatoid arthritis Chrono pharmacotherapy has been recommended to ensure that the highest blood levels of the drug coincide with peak pain and stiffness. Result and discussion: The prepared tablets were characterized and found to exhibit satisfactory physico-chemical characteristics. Hence, the main objective of present work is to formulate FPDDS of meloxicam in order to achieve drug release after pre-determined lag phase. Developed formulations were evaluated for in vitro drug release studies, water uptake and erosion studies, floating behaviour and in vivo radiology studies. Results showed that a certain lag time before drug release which was due to the erosion of the hydrophilic erodible polymer. The lag time clearly depends on the type and amount of hydrophilic polymer which was applied on the inner cores. Floating time and floating lag time was controlled by quantity and composition of buoyant layer. In vivo radiology studies point out the capability of the system of longer residence time of the tablets in the gastric region and releasing the drug after a programmed lag time. Conclusion: The optimized formulation of the developed system provided a lag phase while showing the gastroretension followed by pulsatile drug release that would be beneficial for chronotherapy of rheumatoid arthritis and osteoarthritis.

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

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i9.20423 ◽

2018 ◽

Vol 11 (9) ◽

pp. 305

Author(s):

Chiranjibi Adhikari ◽

Gururaj S Kulkarni ◽

Shivakumar Swamy

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Drug Delivery System ◽

Delivery System ◽

Lag Time ◽

Release Profile ◽

Salbutamol Sulfate ◽

Pulsatile Drug Delivery ◽

Core Tablet

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.

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Formulation and Evaluation of Modified Pulsincap as Pulsatile Drug Delivery System for Treatment of Rheumatoid Arthritis

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2016.9.5.5 ◽

2016 ◽

Vol 9 (5) ◽

pp. 3476-3487

Author(s):

Chavda D Hiral ◽

Sonpal N Rakshit ◽

Paresh Prajapati A ◽

Madhabhai M Patel

Keyword(s):

Rheumatoid Arthritis ◽

Drug Delivery ◽

Drug Release ◽

Drug Delivery System ◽

Delivery System ◽

Phosphate Buffer ◽

Lag Time ◽

Contour Plot ◽

Independent Variables ◽

Pulsatile Drug Delivery

The aim of the present study was to design and evaluate a modified pulsincap pulsatile drug delivery system of etodolac for treatment of rheumatoid arthritis. Capsule body was made water insoluble by cross linking with formaldehyde vapour. It was filled with drug, osmogen NaCl and super disintegrant sodium starch glycolate to expel the drug after predetermined lag time. A hydro gel plug made of HPMC K4M was placed in the capsule body to achieve desired drug release after lag time for chronotherapy of rheumatoid arthritis. Untreated cap was then fitted to the treated body was sealed. Entire unit was coated with 5% Eudragit S-100 to prevent variable gastric emptying. A 32 full factorial design was used for optimization in which concentration ratio of NaCl and SSG (X1), and the weight of hydrogel plug (X2) were selected as independent variables while lag time and t90% were taken as dependent variables. FTIR and DSC studies confirmed drug excipient compatibility. Developed formulation was evaluated for in-vitro drug release in pH 1.2, phosphate buffer pH 6.8 and phosphate buffer pH 7.4. Statistical analysis confirmed the significance of selected independent variables. Response surface plot and contour plot indicate augmentation of the line toward the weight of hydrogel plug factor indicating greater significance. Formulation with highest desirability containing 34.4 mg of SSG, 137.6 mg of NaCl and 48 mg of HPMC K4M plug was selected as an optimized formulation as it provided the desired lag time of 6 hours and t90% of about 477 mins. Accelerated stability study performed on optimized formulation suggested stable and viable formulation. A stable, efficient formulation modified pulsincap of Etodolac as a pulsatile drug delivery system was developed with proposed increased patient compliance and improved dosage form efficiency.

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Formulation and In Vitro Evaluation of Compressed Coated Tablets of Simvastatin for Pulsatile Drug Delivery

International Journal of Pharma and Bio Sciences ◽

10.22376/ijpbs/lpr.2021.11.1.p110-117 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kumari P.V. Kamala ◽

Mounica V. ◽

Rao Y. Srinivasa

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Drug Delivery System ◽

Delivery System ◽

Guar Gum ◽

Lag Time ◽

Blood Cholesterol ◽

In Vitro Dissolution ◽

Pulsatile Drug Delivery

Pulsatile drug delivery system is one type of drug delivery system, where the delivery device is capable of releasing drugs after a predetermined time-delay (i.e. lag time). This system has a peculiar mechanism of delivering the drug rapidly and completely after a "lag time," i.e., a period of "no drug release." These systems are beneficial for drugs having high first-pass effect drugs administered for diseases that follow chrono pharmacological behavior such as drugs having specific absorption sites in GIT, targeting to colon; and cases where nighttime dosing is required. The objective of the present study was to formulate and evaluate a press coated pulsatile drug delivery system of simvastatin in order to attain a time controlled release to lower the blood cholesterol level by releasing the drug with a distinct predetermined lag time of five hrs. Simvastatin is a water insoluble drug and its absorption is dissolution rate limited. The core formulations were composed of simvastatin and disintegrants like lycoat, SSG, ludiflash in different ratios and was coated with xanthan gum, guar gum, HPMC K4M, HPMC K15M as a release modifier. Press coated tablets were evaluated for hardness, friability, drug content, and in vitro drug release. Result of in vitro dissolution study of the prepared tablet suggested that, the release of drug from press coated tablets match with chrono-biological requirement of disease.

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Formulation and Evaluation of Bio-adhesive Pulsatile Drug Delivery System of Telmisartan

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i2.1982 ◽

2020 ◽

Vol 11 (2) ◽

pp. 1282-1287

Author(s):

Patil S. V. ◽

Salokhe P. A. ◽

Patil S. S. ◽

Ustad J. Y. ◽

Shedbale S. S.

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Drug Delivery System ◽

Delivery System ◽

Lag Time ◽

Early Morning ◽

Pulsatile Drug Delivery ◽

Hypertensive Drug ◽

Time Specific ◽

Core Tablet

The main objective of this study was to formulate and evaluate of Bio-adhesive pulsatile drug delivery system of Telmisartan, an anti-hypertensive drug in order to achieve better therapeutic efficacy and patient compliance. The approach of combination of bio-adhesive pulsatile formulation is suitable for gastro retention and time specific drug delivery. The study was carried by preparation of fast disintegrating core tablet followed by incorporation of core tablet to design bio-adhesive pulsatile tablet by press coating. The press coated tablet was prepared with the polymersethyl cellulose and carbopol. The formulation was evaluated for precompression and post compression parameters, lag time, drug release and bio-adhesive study. All evaluation parameters were found within limits. The lag time expected for this disease was 8 hours as need of drug release for this disease was more likely to act in early morning. The 8 hour lag time was obtained in optimized formulation which has shown muco-adhesion for the same period. Thus bio-adhesive pulsatile drug delivery system could be the best precautionary alternative for the drugs having maximum absorption in stomach and used for diseases which follows circadian rhythm.

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Preparation And Evaluation Of ‘3 Cap’pulsatile Drug Delivery System Of Ramipril

Cardiovascular & Hematological Agents in Medicinal Chemistry ◽

10.2174/1871525718666200528140527 ◽

2020 ◽

Vol 18 ◽

Author(s):

Priyanka Kriplani ◽

Kamla Pathak ◽

Anil Philip

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Drug Delivery System ◽

Delivery System ◽

Flow Rate ◽

Circadian Variation ◽

Surface Design ◽

Pulsatile Drug Delivery ◽

Hypertensive Drug ◽

Time Density

Background: Chronotherapeutics, the drug delivery based on circadian rhythm, is recently gaining much attention worldwide. Various diseases like asthma, hypertension, and arthritis show circadian variation that demands time scheduled drug release for effective drug action. So, Pulsatile drug delivery system have been designed to confer preprogrammed drug delivery. Objective: In the present study, a ‘3 Cap’ pulsatile drug delivery system has been developed, optimized and characterized in order to achieve floating and pulsatile release of Ramipril. Methods: An optimal response surface design was employed to investigate the effect of isopropanol: formaldehyde vapours for varying time on drug release from the capsules. ‘3 Cap’ pulsatile drug delivery system was evaluated in terms of floating time, density, effect of gastric flow rate and type of dissolution apparatus on drug release. Results: Independent variables exhibited significant effect on the drug release of the prepared formulations. Results showed that time between the release of fractions of dose increased with increase in formaldehyde: isopropanol ratio and duration of exposure to formaldehyde vapours with no effect of gastric flow rate. Conclusion: The design results revealed that an optimum exposure of 1:2 of isopropanol: formaldehyde vapours for sixty minutes resulted in desired release of second pulse of dose after a predetermined lag time of 5 hours as desired. ‘3Cap’ system was successful in achieving floating and pulsed release of hypertensive drug opening a ‘new lease of life’ to the existing drug molecule.

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Recent Trends in Chronopharmaceutics, Pulsatile Drug Delivery System

Al Mustansiriyah Journal of Pharmaceutical Sciences ◽

10.32947/ajps.19.04.0417 ◽

2019 ◽

pp. 41-49

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Drug Delivery System ◽

Delivery System ◽

Correct Position ◽

Unit System ◽

Recent Trends ◽

Osmotic System ◽

Pulsatile Drug Delivery ◽

Fast Release

Pulsatile Drug Delivery Systems (PDDS) are getting considerable interest in delivering a drug at the correct position, at the correct time, and in the correct quantity, thus offering temporal, spatial, and intelligent delivery with improving patient compliance. These systems are intended to meet body's biological rhythm. Here, the delivery of drugs is assisted by the rhythm of disease. The main reason for the using pulsatile drug release is when the continuous drug release is not required. A PDDS must be designed in such a way that after the lag time a complete and fast release of drugs is achieved. The article deals with various systems such as osmotic system, capsular system, single and multi-unit system based on the utilization of erodible or soluble polymer coating and using of rupturable membrane. These systems are favorable to drugs with chronopharmacological behaviors such as drugs used to treat rheumatoid arthritis, ankylosing spondylitis, and osteoarthritis. The current review paper focus on the causes for pulsatile drug delivery system design, types of illness requiring pulsatile release, classification, benefits, and restriction of this drug delivery system

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Chronomodulated Delivery of Pantoprazole for Nocturnal Hyperacidity

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2015.8.4.7 ◽

2015 ◽

Vol 8 (4) ◽

pp. 3038-3044

Author(s):

Mahalakshmi P ◽

Suriyaprakash T N K ◽

S. Lakshmana Prabu

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Drug Delivery Systems ◽

Lag Time ◽

Delivery Systems ◽

Burst Release ◽

Dependent Manner ◽

Compression Technique ◽

Pulsatile Drug Delivery

The objective of this work was to design and evaluate an oral site-specific, pulsatile drug delivery system containing Pantoprazole sodium which can be targeted to colon in a pH and time dependent manner, to modulate the drug level in synchrony with the circadian rhythm of nocturnal hyperacidity. Five different composition of Core tablets were prepared by direct compression technique. Based on the release studies of core tablets, nine different compositions of press coated tablets were prepared and analyzed. The press coated tablet further coated by using five different proportions of Eudragit RS PO for providing consistent, reproducible chronomodulated release profile. Formulation FPC3 is more suitable among the formulations to design pulsatile release formulations of pantoprazole sodium for 6 hours lag time. After this lag time burst release was observed which exhibited sigmodial release pattern and that was considered to be an ideal for the pulsatile drug delivery system. The chronomodulated drug delivery systems for pantoprazole sodium for the treatment of hyperacidity was successfully developed and the release of the drug was sharp and complete after the lag time which is necessary for any pulsatile drug delivery systems.

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PULSATILE DRUG DELIVERY SYSTEM: A FORMULATION APPROACH FOR TREATMENT OF DISEASES

International Journal of Current Pharmaceutical Research ◽

10.22159/ijcpr.2020v12i3.38328 ◽

2020 ◽

pp. 16-21

Author(s):

PASHAM SOWMYA ◽

VENKATESH DP ◽

SUJIT NAYEK

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Drug Delivery Systems ◽

Biological Rhythms ◽

Lag Time ◽

Dosage Forms ◽

Delivery Systems ◽

Continuous Release ◽

Pulsatile Drug Delivery

location at a particular time. Some of the conditions under which pulsatile drug delivery system is positive include duodenal ulcer, cardiovascular disease, arthritis, asthma, diabetes, neurological disorder, cancer, hypertension, and hypercholesterolemia. Pulsatile drug delivery systems are essentially time-controlled drug delivery systems in which the lag time is regulated independently of environmental factors such as pH, enzymes, gastrointestinal motility, etc. The theory justification for the use of pulsatile release is for drugs where a continuous release of drugs is not needed, i.e. a zero-order release. Drug administration in chronopharmacotherapy is coordinated with biological rhythms to achieve full therapeutic effect and minimize harm to the patient. This drug delivery system is designed to distribute drugs in accordance with body clock. The pulse must be designed in such a way as to achieve a total and rapid release after the lag time. Pulsatile drug delivery is therefore one device that provides strong promises of benefit to patients suffering from chronic conditions such as arthritis, asthma, hypertension by delivering medication at the right time, right place and in appropriate quantities. In recent pharmaceutical applications involving pulsatile delivery; multi-particulate dosage forms (e. g. pellets) over single-unit dosage forms are gaining more popularity. On the basis of methodologies, various pulsatile technologies have been developed, including ACCU-BREAKTM, AQUALON, CODAS ®, PRODAS ®, SODAS ®, MINITABS ®, DIFFUCAPS ®, OROS ® etc.

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NOVEL FLOATING AGENT SACCHAROMYCES BOULARDII FORMULATION BASED FLOATING DRUG DELIVERY SYSTEM

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2021v13i5.42237 ◽

2021 ◽

pp. 223-229

Author(s):

SUVARNA CHITTAM ◽

ASHOK BHOSALE

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Calcium Hydroxide ◽

Drug Delivery System ◽

Delivery System ◽

Lag Time ◽

Saccharomyces Boulardii ◽

Floating Drug Delivery ◽

Floating Tablet ◽

Floating Drug Delivery System

Objective: The objective is to design and optimize a floating tablet of furosemide using a novel floating agent Saccharomyces boulardii. Methods: In this study floating tablet based on principle of combination of floating and swelling prepared by direct compression technique. Saccharomyces boulardii probiotics preparation is used as a floating agent due to its bloating property i.e. production of CO2 gas and hydrophilic polymer HPMC E LV 15 used as swellable polymer. Furosemide is a BCS class IV drug selected as model drug which shows pH dependent solubility and permeability and it is better absorbed from the gastric region, hence to improve dissolution and residence at absorption site of such drug, floating drug delivery system is needed. Calcium hydroxide used as pH modifier which increase rate of dissolution of furosemide and also maintain integrity of tablet matrix. Formulation designed and developed using central composite design response surface methodology technique, so as to explore the effect of formulation variables such as amount of Saccharomyces boulardii preparation and calcium hydroxide on floating lag time and % drug release after 12h. Results: The numerical and graphical optimization technique were used to choose the optimal formulation. Floating lag time was found to be 12.6 min and 88.18% drug release for the optimized formulation. In vivo buoyancy studies depicted that formulation stay more then 6h in stomach. Conclusion: Study indicate that Saccharomyces boulardii is a promising floating agent, and the formulation containing this novel floating agent is suitable for gastro retention and it increases bioavailability of furosemide.

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