Formulation Development and Characterization of controlled release core in cup matrix tablets of venlafaxine HCl

Background: Venlafaxine HCl is a selective serotonin reuptake inhibitor which is given in the treatment of depression. The delivery of the drug at a controlled rate can be of great importance for prolonged effect. Objective: The objective was to prepare and optimize the controlled release core in cup matrix tablet of venlafaxine HCl using the combination of hydrophilic and hydrophobic polymers to prolong the effect with rate controlled drug release. Methods: The controlled release core in cup matrix tablets of venlafaxine HCl were prepared using HPMC K5, K4, K15, HCO, IPA, aerosol, magnesium sterate, hydrogenated castor oil and micro crystalline cellulose PVOK-900 using wet granulation technique. Total ten formulations with varying concentrations of polymers were prepared and evaluated for different physicochemical parameters such FTIR analysis for drug identification, In-vitro drug dissolution study was performed to evaluate the amount of drug release in 24 hrs, drug release kinetics study was performed to fit the data in zero order, first order, Hixson–crowell and Higuchi equation to determine the mechanism of drug release and stability studies for 3 months as observed. Results: The results of hardness, thickness, weight variation, friability and drug content study were in acceptable range for all formulations. Based on the In vitro dissolution profile, formulation F-9 was considered to be the optimized extending the release of 98.32% of drug up to 24 hrs. The data fitting study showed that the optimized formulation followed the zero order release rate kinetics and also compared with innovator product (flavix XR) showed better drug release profile. Conclusion: The core-in-cup technology has a potential to control the release rate of freely water soluble drugs for single administration per day by optimization with combined use of hydrophilic and hydrophobic polymers.

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Formulation and Evaluation of Nelfinavir Extended Release Trilayer Matrix Tablets by Design of Experiment

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2018.11.5.6 ◽

2018 ◽

Vol 11 (5) ◽

pp. 4259-4268

Author(s):

Nirmala Rangu ◽

Gande Suresh

Keyword(s):

Controlled Release ◽

Drug Release ◽

Hydroxypropyl Methylcellulose ◽

Magnesium Stearate ◽

Zero Order ◽

Matrix Tablets ◽

Drug Dissolution ◽

Crystalline Cellulose ◽

Dissolution Profile ◽

Release Formulation

The present study was aimed to develop once-daily controlled release trilayer matrix tablets of nelfinavir to achieve zero-order drug release for sustained plasma concentration. Nelfinavir trilayer matrix tablets were prepared by direct compression method and consisted of middle active layer with different grades of hydroxypropyl methylcellulose (HPMC), PVP (Polyvinyl Pyrrolidine) K-30 and MCC (Micro Crystalline Cellulose). Barrier layers were prepared with Polyox WSR-303, Xanthan gum, microcrystalline cellulose and magnesium stearate. Based on the evaluation parameters, drug dissolution profile and release drug kinetics DF8 were found to be optimized formulation. The developed drug delivery system provided prolonged drug release rates over a period of 24 h. The release profile of the optimized formulation (DF8) was described by the zero-order and best fitted to Higuchi model. FT-IR studies confirmed that there were no chemical interactions between drug and excipients used in the formulation. These results indicate that the approach used could lead to a successful development of a controlled release formulation of nelfinavir in the management of AIDS.

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Formulation Study and Evaluation of Matrix and Three-Layer Matrix Tablets Oral Controlled Drug Delivery System Based on Xanthan Gum and Locust Bean Gum

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2010.3.2.15 ◽

2010 ◽

Vol 3 (2) ◽

pp. 1006-1014

Author(s):

Y. Madhusudan Rao ◽

S L Ahmed ◽

M L Narsu ◽

S J Mohan

Keyword(s):

Drug Release ◽

Xanthan Gum ◽

Zero Order ◽

Water Soluble ◽

Matrix Tablets ◽

Crystalline Cellulose ◽

Locust Bean Gum ◽

The Matrix ◽

Locust Bean ◽

Diltiazem Hcl

The present study was carried out to develop oral controlled release matrix tablets and three layer matrix tablets of highly water soluble diltiazem HCl using natural polymers Xanthan gum (XG), locust bean gum (LBG) and a mixture XG: LBG in 1:1 ratio as matrix forming agent, and anionic Sodium Carboxyl Methyl Cellulose as release retardant layer on the matrix core, Di calcium Phosphate (DCP) and Micro crystalline Cellulose (MCC) as fillers. Matrix core tablets were prepared with by granulation technique.The characterization of physical mixture of drug and excipeints was performed by infra red spectroscopy. The finding of the study indicated that the matrix tablets prolonged the release, but predominantly in a first order fashion, layering with SCMC granules on the matrix core, provided linear drug release with zero order kinetics. The influence of layers on matrix core and release rate was described by the peppas equation, model independent approach, Mean dissolution time (MDT) and dissolution efficiency (D.E 8%). The addition of SCMC layers on the matrix core could notably influence the dissolution behavior and mechanism of drug release. Increasing the quantity of layers caused decreased values of k and increased n value, in a linear relationship. MDT for matrix tablet (S6) and three layer matrix tablets (S6L3) was found to be 5.16h and 11.97h, D.E 8% was 76.23% and 66.21% respectively. These indicated that the release of drug is slower from the three layer matrix tablets. Type of fillers has a limited effect on the drug release mechanism from matrix tablets. Stability studies revealed that the formulation was stable at 45°±2°C and 75±5%RH. Hence natural polymer as matrix core and anionic polymer SCMC as retardant layer in the form of three layer matrix tablets provided the zero order release of highly water soluble Diltiazem HCl.

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Polymer Distribution and Mechanism Conversion in Multiple Media of Phase-Separated Controlled-Release Film-Coating

Pharmaceutics ◽

10.3390/pharmaceutics11020080 ◽

2019 ◽

Vol 11 (2) ◽

pp. 80 ◽

Cited By ~ 4

Author(s):

Lu Chen ◽

Guobao Yang ◽

Xiaoyang Chu ◽

Chunhong Gao ◽

Yuli Wang ◽

...

Keyword(s):

Controlled Release ◽

Drug Release ◽

Release Rate ◽

Water Soluble ◽

Drug Dissolution ◽

Acetate Buffer ◽

Drug Solubility ◽

Drug Release Rate ◽

The Media ◽

Multiple Media

Phase-separated films of water-insoluble ethyl cellulose (EC) and water-soluble hydroxypropyl cellulose (HPC) can be utilized to tailor drug release from coated pellets. In the present study, the effects of HPC levels and the pH, type, ionic strength and osmolarity of the media on the release profiles of soluble metoprolol succinates from the EC/HPC-coated pellets were investigated, and the differences in drug-release kinetics in multiple media were further elucidated through the HPC leaching and swelling kinetics of the pellets, morphology (SEM) and water uptake of the free films and the interaction between the coating polymers and the media compositions. Interestingly, the drug release rate from the pellets in different media was not in agreement with the drug solubility which have a positive correlation with the drug dissolution rate based on Noyes–Whitney equation law. In particular, the drug release rate in acetate buffer at pH 4.5 was faster than that in other media despite the solubility of drug was relatively lower, regardless of the HPC levels. It may be attributed to the mutual effect between the EC and acetate buffer, which improved the permeability of the film. In contrast, the release of drug in HCl solution was dependent on the HPC levels. Increasing the levels of HPC increased the effects of hydrogen ions on the polymer of HPC, which resulted in a lower viscosity and strength of the gel, forming the larger size of pores in polymer films, thus increasing the drug diffused from the coating film. Further findings in phosphate buffer showed a reduction in the drug release compared to that in other media, which was only sensitive to the osmolarity rather than the HPC level and pH of the buffer. Additionally, a mathematical theory was used to better explain and understand the experimentally measured different drug release patterns. In summary, the study revealed that the effects of the media overcompensated that of the drug solubility to some extent for controlled-release of the coating polymers, and the drug release mechanism in multiple media depend on EC and HPC rather than on HPC alone, which may have a potential to facilitate the optimization of ideally film-coated formulations.

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POROUS PLASTIC MATRIX TABLETS OF LEVETIRACETAM FOR ZERO-ORDER CONTROLLED RELEASE: DEVELOPMENT AND FORMULATION OPTIMIZATION

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2021v13i4.41172 ◽

2021 ◽

pp. 135-141

Author(s):

RAVI PARIMI ◽

RAMA RAO VADAPALLI ◽

K. E. PRAVALLIKA

Keyword(s):

Controlled Release ◽

Drug Release ◽

Research Work ◽

Zero Order ◽

Water Soluble ◽

Matrix Tablets ◽

Peg 6000 ◽

Study Results ◽

Plastic Matrix ◽

Porous Plastic

Objective: The prior objective of the current research work was to develop once-daily levetiracetam extended/controlled-release tablets having zero-order release kinetics with the plastic matrix as the release retarding element. For a high water-soluble drug, the formulation of a dosage form so as to have an extended drug release has always been a difficult task. Methods: In the current work, levetiracetam which is a highly soluble drug was taken as the model drug for which extended-release matrix tablets were developed using varied plastic polymers like Polyvinyl acetate (PVAc), Polyvinyl chloride (PVC), Eudragit RSPO and Eudragit RLPO. PVP was considered as a pore-forming agent and PEG 6000 was taken as a water regulating agent. The porous plastic matrix tablets were prepared by embedding the drug in solvent-activated polymer dispersion followed by drying, sieving, mixing with other excipients and finally compressed. Including physical characterization studies and drug release studies, the tablets were subjected to SEM studies before and after the dissolution studies to analyze the effect of the pore former. Results: Pre-compression mixtures exhibited good packageability of 81-92% and hence the compressed tablets were strong enough with good tensile strength in the range of 0.78–0.90 N/mm2. Drug release study results showed that the drug release was controlled for a period of 12–24h. PVAc had shown better controlled-release among all the plastic polymers taken. PEG 6000 in combination with PVP produced the desired zero-order drug release. Conclusion: The levetiracetam porous plastic matrix tablets were developed with zero-order drug release that was effectively controlled for 24hr.

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Development and Evaluation of Controlled Release Mucoadhesive Tablets of Captopril

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2016.9.3.8 ◽

1970 ◽

Vol 9 (3) ◽

pp. 3318-3329

Author(s):

Kranthi Kumar Kotta ◽

L. Srinivas

Keyword(s):

Controlled Release ◽

Drug Release ◽

Xanthan Gum ◽

Diffusion Mechanism ◽

Matrix Tablets ◽

Fickian Diffusion ◽

Content Uniformity ◽

In Vitro Drug Release ◽

Mucoadhesive Tablets

The present investigation focuses on the development of mucoadhesive tablets of captopril which are designed to prolong the gastric residence time after oral administration. Matrix tablets of captopril were formulated using four mucoadhesive polymers namely guar gum, xanthan gum, HPMC K4M and HPMC K15M and studied for parameters such as weight variation, thickness, hardness, content uniformity, swelling index, mucoadhesive force and in vitro drug release. Tablets formulated Xanthan gum or HPMC K4M with HPMC K15M provide slow release of captopril over period of 12 hr and were found suitable for maintenance portion of oral controlled release tablets. The cumulative % of drug release of formulation F9 and F10 were 90 and 92, respectively. In vitro release from these tablets was diffusion controlled and followed zero order kinetics. The ‘n’ values obtained from the pappas-karsemeyer equation suggested that all the formulation showed drug release by non-fickian diffusion mechanism. Tablets formulated Xanthan gum or HPMC K4M with HPMC K15M (1:1) were established to be the optimum formulation with optimum bioadhesive force, swelling index & desired invitro drug release. This product was further subjected to stability study, the results of which indicated no significant change with respect to Adhesive strength and in vitro drug release study.

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In vitro and in vivo evaluation of controlled-release matrix tablets of highly water-soluble drug applying different mw polyethylene oxides (PEO) as retardants

Drug Development and Industrial Pharmacy ◽

10.1080/03639045.2017.1405429 ◽

2017 ◽

Vol 44 (4) ◽

pp. 544-552 ◽

Cited By ~ 5

Author(s):

Haoyang Wen ◽

Xue Li ◽

Yuenan Li ◽

Haiying Wang ◽

Yanyan Wang ◽

...

Keyword(s):

Controlled Release ◽

Water Soluble ◽

Matrix Tablets ◽

In Vivo Evaluation ◽

Polyethylene Oxides ◽

Water Soluble Drug

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DESIGN AND EVALUATION OF CONTROLLED-RELEASE OCULAR INSERTS OF BRIMONIDINE-TARTRATE AND TIMOLOL MALEATE

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i1.15199 ◽

2016 ◽

Vol 9 (1) ◽

pp. 79 ◽

Cited By ~ 2

Author(s):

Preethi G. B. ◽

Prashanth Kunal

Keyword(s):

Controlled Release ◽

Drug Release ◽

Sodium Alginate ◽

Calcium Chloride ◽

Release Kinetics ◽

Water Soluble ◽

Moisture Loss ◽

Timolol Maleate ◽

Brimonidine Tartrate

Objective: The current work was attempted to formulate and evaluate a controlled-release matrix-type ocular inserts containing a combination of brimonidine tartrate and timolol maleate, with a view to sustain the drug release in the cul-de-sac of the eye.Methods: Initially, the infrared studies were done to determine the drug–polymer interactions. Sodium alginate-loaded ocuserts were prepared by solvent casting technique. Varying the concentrations of polymer—sodium alginate, plasticizer—glycerine, and cross-linking agent—calcium chloride by keeping the drug concentration constant, made a total of nine formulations. These formulations were evaluated for its appearance, drug content, weight uniformity, thickness uniformity, percentage moisture loss, percentage moisture absorption, and in vitro release profile of the ocuserts. Finally, accelerated stability studies and the release kinetics were performed on the optimised formulation.Results: It was perceived that polymer, plasticizer, and calcium chloride had a significant influence on the drug release. The data obtained from the formulations showed that formulation—F9 was the optimised formulation, which exhibited better drug release. The release data of the optimised formulation tested on the kinetic models revealed that it exhibited first-order release kinetics. Conclusion: It can be concluded that a natural bioadhesive hydrophilic polymer such as sodium alginate can be used as a film former to load water soluble and hydrophilic drugs like brimonidine tartrate and timolol maleate. Among all formulations, F9 with 400 mg sodium alginate, 2% calcium chloride and 60 mg glycerin were found to be the most suitable insert in terms of appearance, ease of handling, thickness, in vitro drug release and stability.

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Optimizing the Role of Polymer Blend in the Preparation of Acyclovir Controlled-Release Tablets: An Approach for Better Patient Compliance

10.20944/preprints201807.0165.v1 ◽

2018 ◽

Author(s):

Barkat Khan ◽

Faheem Haider ◽

Kifayat Shah ◽

Bushra Uzair ◽

Kaijian Hou ◽

...

Keyword(s):

Controlled Release ◽

Drug Release ◽

Release Kinetics ◽

Immediate Release ◽

Matrix Tablets ◽

Release Mechanism ◽

In Vitro Drug Release ◽

Solubility Study ◽

Release Data

This study was carried out to formulate and evaluate controlled release (CR) matrix tablets of Acyclovir using combination of hydrophilic and hydrophobic polymers. Acyclovir is a guanine derivative and is its half-life is short hence administered five times a day using immediate release tablets. Six formulations (F1-F6) were developed using Ethocel and Carbopol in equal combinations at drug-polymer (D:P) ratio of 10:5, 10:6, 10:7, 10:8, 10:9 and 10:10. Solubility study was performed using six different solvents. The compatibility studies were carried out using FTIR and DSC. According to USP, Quality Control and dimensional tests (hardness, friability, disintegration and thickness) were executed. In-vitro drug release studies of Acyclovir was carried out in dissolution apparatus using using 0.1 N HCl medium at constant temperature of 37 ± 0.5 ºC. In order to analyze the drug release kinetics, five different mathematical models were applied to the release data. The results showed that there was no incompatibility between drug and polymers. Physical QC tests were found within limits of USP. The release was retarded upto 24 hrs and non-fickian in-vitro drug release mechanism was found. A formulation developed using blend of polymers, showed excellent retention and desired release profiles thus providing absolute control for 24 hrs.

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Preparation of Biodegradable Silk Fibroin/Alginate Blend Films for Controlled Release of Antimicrobial Drugs

Advances in Materials Science and Engineering ◽

10.1155/2013/412458 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 18

Author(s):

Yaowalak Srisuwan ◽

Yodthong Baimark

Keyword(s):

Controlled Release ◽

Drug Release ◽

Silk Fibroin ◽

Water Soluble ◽

Drug Release Profile ◽

Sem Images ◽

Blend Ratio ◽

Blend Films ◽

Vis Spectroscopy

Silk fibroin (SF)/alginate blend films have been prepared for controlled release of tetracycline hydrochloride, an antimicrobial model drug. The blend films were analysed by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and UV-vis spectroscopy. The functional groups of the SF/alginate blends were monitored from their FTIR spectra. The homogeneity of the blend films was observed from SEM images. The dissolution and film transparency of the blend films depended on the SF/alginate blend ratio. Thein vitrodrug release profile of the blend films was determined by plotting the cumulative drug release versus time. It was found that the drug release significantly decreased as the SF/alginate blend ratio increased. The results demonstrated that the SF/alginate blend films should be a useful controlled-release delivery system for water-soluble drugs.

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