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

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.

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

2020 ◽  
Vol 15 ◽  
Author(s):  
Balaji Maddiboyina ◽  
Vikas Jhawat ◽  
Gandhi Sivaraman ◽  
Om Prakash Sunnapu ◽  
Ramya Krishna Nakkala ◽  
...  
Keyword(s):  
Controlled Release ◽  
Drug Release ◽  
Release Rate ◽  
Zero Order ◽  
Water Soluble ◽  
Matrix Tablets ◽  
Drug Dissolution ◽  
Crystalline Cellulose ◽  
Hydrophobic Polymers

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.

scholarly journals Development and in vivo Evaluation of Nelfinavir Extended Release Trilayer Matrix Tablets in the Management of AIDS

2018 ◽  
Vol 10 (4) ◽  
Author(s):  
Rangu Nirmala ◽  
Gande Suresh
Keyword(s):  
Drug Release ◽  
Extended Release ◽  
Hydroxypropyl Methylcellulose ◽  
Controlled Drug Release ◽  
Magnesium Stearate ◽  
Matrix Tablets ◽  
Drug Dissolution ◽  
Dissolution Profile ◽  
In Vivo Evaluation

The purpose of this investigation was to design and develop trilayer matrix tablets of Nelfinavir prepared by direct compression method and consisted of middle active layer with different grades of hydroxypropyl methylcellulose (HPMC), PVK K 30 and MCC. Barrier layers are 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 was 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. From in vivo bioavailability studies the extended release of Nelfinavir from trilayer matrix tablets also provides for higher plasma drug content and improved bioavailability. The results indicate that the approach used could lead to a successful development of low biological half life Nelfinavir with controlled drug release in the effective management of AIDS.

scholarly journals Design and in vivo Evaluation of Controlled Release Gliclazide Trilayer Matrix Tablets in the Management of Diabetes Mellitus

2018 ◽  
Vol 10 (05) ◽  
Author(s):  
D.V.R.N. Bhikshapathi ◽  
B. Ram Prasad
Keyword(s):  
Diabetes Mellitus ◽  
Plasma Concentration ◽  
Controlled Release ◽  
Drug Release ◽  
Drug Concentration ◽  
Hydroxypropyl Methylcellulose ◽  
Physicochemical Characteristics ◽  
Matrix Tablets ◽  
Dissolution Profile

The purpose of the present study was to develop and optimize multi-layered matrix tablets of Gliclazide trilayer tablets to achieve zero-order drug release for sustained plasma concentration. Gliclazide tablets were prepared by direct compression and consist of middle active layer with different grades of hydroxypropyl methylcellulose (HPMC K 4M, K 15M and K100M), Guar gum and Eudragit L 100. The tablets were also evaluated for physicochemical characteristics and release kinetics. The physicochemical characteristics of the prepared tablets were satisfactory. The developed drug delivery systems showed prolonged drug release rates over a period of 24 h. In vivo bioavailability studies were carried out on the optimized formulation (EF14), mean time to attain peak drug concentration (Tmax) was 6.00 ± 0.14 and 4.02 ± 0.12 h for the optimized and marketed product respectively, while mean maximum drug concentration (Cmax) was 124.80 ± 1.02 ng/ml and 95.12 ± 1.05 ng/ml respectively. AUC0-α and AUC0-t for optimized formulation was significantly higher (p less than 0.05) as compared to marketed product. A fair correlation between the dissolution profile and bioavailability for the optimized formulation was observed. The results indicate that the approach used could lead to a successful development of a controlled release formulation of the drug. The EF14 was shown significant plasma concentration with controlled release and maintained for 24 hours with patient compliance by reducing the dosage frequency, when compared with marketed product in the efficient management of Diabetes mellitus.

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

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. 

scholarly journals Effect of Channeling Agents on the Release Profile of Theophylline from METHOCEL K4M Based Matrix tablets

1970 ◽  
Vol 7 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Md Shaikhul Millat Ibn Razzak ◽  
Ferdous Khan ◽  
Md Ziaur Rahman Khan ◽  
Kanij Fatema ◽  
Muhammed Shahidul Islam ◽  
...  
Keyword(s):  
Drug Release ◽  
Release Rate ◽  
Release Profile ◽  
Matrix Tablets ◽  
Drug Dissolution ◽  
Release Mechanism ◽  
Dissolution Profile ◽  
Compression Process ◽  
Low Viscosity ◽  
Time Required

The present study was undertaken to investigate the effect of channeling agents on the release profile of Theophylline from METHOCEL K4M based matrix systems. Matrix tablets of Theophylline using METHOCEL K4M were prepared by direct compression process. METHOCEL K4M polymer is hydrophilic in nature. NaCl and PEG 1500 were used as channeling agents. Drug release study was evaluated for eight hours using USP 22 paddletype dissolution apparatus using distilled water as the dissolution medium. The release mechanisms were explored and explained with zero order, Higuchi and Korsmeyer equations. The release rate, extent and mechanisms were found to be governed by channeling agent type and content. Higher channeling agent content (42.49%) in the matrix increased the rate and extent of the drug release because of increased porosity in the tablet matrices, at lower channeling agent (19.76%) level, the rate and extent of drug release was decreased and in absence of channeling agents these were least. NaCl ensures maximum release of drug from low viscosity grade METHOCEL K4M than PEG 1500 when other parameters were kept constant. It was found that type and amount of channeling agent significantly affect the time required for 50% of drug release (T50%), percentage drug release at 8 hours, release rate constant (K) and diffusion exponent (n). Kinetic modeling of dissolution profiles revealed drug release mechanism ranges from diffusion controlled or Fickian transport to anomalous type or non-Fickian transport, which was mainly dependent on the presence of type and amount of channeling agent. These studies indicate that the proper balance between a matrix forming agent and a channeling agent can produce a drug dissolution profile similar to a theoretical dissolution profile.Key words: Channeling agent, Theophylline, Release Profile, Methocel K4MDOI = 10.3329/dujps.v7i1.1214Dhaka Univ. J. Pharm. Sci. 7(1): 27-32, 2008 (June)

scholarly journals Formulation of Once a Day Controlled Release Tablet of Indomethacin Based on HPMC-Mannitol

1970 ◽  
Vol 4 (1) ◽  
pp. 55-67 ◽  
Author(s):  
Roshan Pradhan ◽  
Uttam Budhathoki ◽  
Panna Thapa
Keyword(s):  
Controlled Release ◽  
Hydroxypropyl Methylcellulose ◽  
Reference Sample ◽  
Methyl Cellulose ◽  
Matrix Tablets ◽  
In Vitro Dissolution ◽  
Matrix Tablet ◽  
Dissolution Profile ◽  
Key Words Indomethacin ◽  
Viscosity Grade

p>A hydroxypropyl methylcellulose (HPMC K4M, HPMC K15M, and HPMC K100M) matrix tablet containing Indomethacin along with mannitol was formulated as a function of HPMC viscosity, and was compared with the commercial products. The release characteristics of the matrix tablet were investigated in the intestinal fluid, 6.8 pH phosphate buffer for 12 hours. The formulated products and two marketed products as reference sample were studied for its different physicochemical parameters and in vitro dissolution studies. It was found that the drug release profile decreases with increase in viscosity of polymer and, with increase polymer level in the formulations. Matrix tablets formulated employing Drug:HPMC K15M:mannitol::1:0.25:1 and Drug:HPMC K15M:mannitol::1:0.25:2 gave slow release of indomethacin spread over 12 hours and their dissolution profiles were compared with the Indian marketed product. The dissolution profiles of both the formulations were similar to the dissolution profile of the marketed product, the similarity factor being 74.59 and 68.04 respectively. The dissolution profiles of formulations containing same viscosity grade of HPMC in remarkably different concentrations and different viscosity grade of HPMC in same concentrations were different. Key words: Indomethacin; Controlled release; Hydroxypropyl methyl cellulose; Mannitol; Dissolution. DOI: 10.3126/kuset.v4i1.2884 Kathmandu University Journal of Science, Engineering and Technology Vol.4, No.1, September 2008, pp 55-67

scholarly journals DESIGN OF CONTROLLED RELEASE MUCOADHESIVE BUCCAL TABLETS OF IVABRADINE HCL USING SINTERING TECHNIQUE

2021 ◽  
pp. 192-203
Author(s):  
CHANDAN MOHANTY ◽  
K. V. SUBRAHMANYAM
Keyword(s):  
Controlled Release ◽  
Drug Release ◽  
Ex Vivo ◽  
Diffusion Mechanism ◽  
Hydroxypropyl Methylcellulose ◽  
Fickian Diffusion ◽  
In Vitro Dissolution ◽  
Dissolution Profile ◽  
Stability Studies ◽  
Buccal Tablets

Objective: The objective of the present work was to study the use of the sintering technique, a relatively new concept in pharmaceutical sciences, in the development of mucoadhesive buccal tablets for ivabradine Hydrochloride. Methods: The method consisted of blending drug, hydroxypropyl methylcellulose (HPMC K100M), carnauba wax, and other excipients followed by direct compression into tablets. The compressed fluffy matrices were sintered at two different constant temperatures like 50 °C and 60 °C for two different periods like 1.5 h and 3 h in a hot air oven. The effect of sintering on tensile strength, dissolution profile, and other parameters were studied. The drug-polymer-excipient compatibility was evaluated by Fourier transform Infrared (FTIR) and differential scanning calorimetric (DSC) studies. Results: The sintering condition markedly affected the drug release properties, hardness, and friability of the tablets. Based on the f2 similarity factor value, Ex-vivo mucoadhesive strength, Ex-vivo residence time, and in vitro dissolution studies, formulation F3SD was selected as an optimized formulation. Drug release followed a non-Fickian diffusion mechanism with the Higuchi model release kinetics. Stability studies of mucoadhesive buccal tablets in normal human saliva indicated the stability of the drug and buccal tablet in the oral cavity. Stability studies as per ICH guidelines revealed that optimized formulation was stable on storage conditions. Conclusion: The sintering technique provides a significant and convenient method for the development of a controlled release dosage form that can be used in the design of mucoadhesive buccal tablets of Ivabradine HCL.

scholarly journals Development and in vitro Evaluation of Sustained Release Matrix Tablets of Indapamide from Methocel® K15 MCR and K100 LVCR

2012 ◽  
Vol 10 (2) ◽  
pp. 87-92
Author(s):  
Utpal Das ◽  
Shimul Halder ◽  
Abul Kalam Lutful Kabir ◽  
Harun Or Rashid ◽  
Abu Shara Shamsur Rouf
Keyword(s):  
Drug Release ◽  
Release Kinetics ◽  
Hydroxypropyl Methylcellulose ◽  
Zero Order ◽  
Matrix Tablets ◽  
Release Mechanism ◽  
Medium Ph ◽  
First Order ◽  
Compressibility Index

Indapamide, a low-dose thiazide-type diuretic, is used for the treatment of essential hypertension. In this study, we developed an indapamide sustained release formulation using Methocel K15 MCR (a modified    hydroxypropyl methylcellulose), Methocel K100 LVCR (a modified hydroxypropyl methylcellulose), magnesium stearate, talc and starch 1500 by direct compression. The powders for tableting were evaluated for angle of repose, loose bulk density, tapped bulk density, compressibility index, total porosity etc. The tablets were subjected to thickness, weight variation test, hardness, friability and in vitro release studies. The in vitro dissolution study was carried out in the gastric medium (pH 1.3) for first two hours and then in the intestinal medium (pH 6.8) for 22 hours using United States Pharmacopoeia (USP) 22 paddle-type dissolution apparatus. The granules showed satisfactory flow properties, compressibility index etc. All the tablets complied with pharmacopoeial specifications. The results of    dissolution studies indicated that the formulation F-5 and F-7 (up to 75.36 % drug release in 12 hours) could extend the drug release up to 12 hours. The drug release patterns were simulated in different kinetic orders such as Zero Order release kinetics, First Order release kinetics, Higuchi release kinetics, Korsmeyer-Peppas release kinetics and Hixson-Crowell release kinetics to assess the release mechanism. From the study we observed that Higuchi release    kinetics was the predominant release mechanism than Zero Order and First Order kinetics. The drug release mechanism from the matrix tablets was found to be non Fickian mechanism.   DOI: http://dx.doi.org/10.3329/dujps.v10i2.11785   Dhaka Univ. J. Pharm. Sci. 10(2): 87-92, 2011 (December)  

scholarly journals Comparative Evaluation of HPMC, PVA and Gelatin as Matrices for Controlled Release Drug Delivery

1970 ◽  
Vol 2 (1) ◽  
pp. 51-55
Author(s):  
Mohammad Anwarul Basher ◽  
Abul Kalam Lutful Kabir ◽  
Mohammad Musarraf Hussain ◽  
Mir Mohammad Abdullah Al Mamun
Keyword(s):  
Controlled Release ◽  
Drug Release ◽  
Diclofenac Sodium ◽  
Magnesium Stearate ◽  
Matrix Tablets ◽  
Matrix Tablet ◽  
Pharmaceutical Sciences ◽  
Drug Release Profile ◽  
Compression Process ◽  
Model Drug

The present study was undertaken to compare three different polymeric gums- HPMC, PVA and gelatin as controlled release matrices. Diclofenac sodium, a potent analgesic, was used as the model drug. Different ratio of HPMC, PVA and gelatin were incorporated into the lactose loaded Diclofenac tablet to explore their impact on drug release. Matrix tablets of Diclofenac were prepared by using individual polymer with magnesium stearate and aerosil by direct compression process at 5 ton pressure. The release of drug from these matrices was studied over 2 hrs in acidic media where insignificant release was observed. Then, the same formulations were studied over 8 hours in buffer media of pH 6.8 at a temperature of 37± 0.5°C. Statistically significant differences in drug release profile was found among the tablets prepared from different matrices. The study revealed that the average % release of drug from different types of polymer loaded matrix tablet varied with the ratio of different polymers. Among the three polymers, PVA showed best dissolution pattern. A comparison of Higuchi curve and bi-exponential curve was also performed. Key words: HPMC; PVA; Gelatin; Controlled release; Diclofenac DOI: 10.3329/sjps.v2i1.5816Stamford Journal of Pharmaceutical Sciences Vol.2(1) 2009: 51-55

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

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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