scholarly journals Development and Bio-Predictive Evaluation of Biopharmaceutical Properties of Sustained-Release Tablets with a Novel GPR40 Agonist for a First-in-Human Clinical Trial

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 804
Author(s):  
Ewelina Juszczyk ◽  
Kamil Kisło ◽  
Paweł Żero ◽  
Ewa Tratkiewicz ◽  
Maciej Wieczorek ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Sustained Release ◽  
Development Strategy ◽  
Matrix Tablets ◽  
Matrix Tablet ◽  
Mechanical Agitation ◽  
Development Cycle ◽  
Dissolution Tests ◽  
Sustained Release Tablets ◽  
Biopharmaceutical Properties

Sustained-release (SR) formulations may appear advantageous in first-in-human (FIH) study of innovative medicines. The newly developed SR matrix tablets require prolonged maintenance of API concentration in plasma and should be reliably assessed for the risk of uncontrolled release of the drug. In the present study, we describe the development of a robust SR matrix tablet with a novel G-protein-coupled receptor 40 (GPR40) agonist for first-in-human studies and introduce a general workflow for the successful development of SR formulations for innovative APIs. The hydrophilic matrix tablets containing the labeled API dose of 5, 30, or 120 mg were evaluated with several methods: standard USP II dissolution, bio-predictive dissolution tests, and the texture and matrix formation analysis. The standard dissolution tests allowed preselection of the prototypes with the targeted dissolution rate, while the subsequent studies in physiologically relevant conditions revealed unwanted and potentially harmful effects, such as dose dumping under an increased mechanical agitation. The developed formulations were exceptionally robust toward the mechanical and physicochemical conditions of the bio-predictive tests and assured a comparable drug delivery rate regardless of the prandial state and dose labeled. In conclusion, the introduced development strategy, when implemented into the development cycle of SR formulations with innovative APIs, may allow not only to reduce the risk of formulation-related failure of phase I clinical trial but also effectively and timely provide safe and reliable medicines for patients in the trial and their further therapy.

Effects of release modifier on Carvedilol release from Kollidon SR based matrix

2012 ◽  
Vol 1 (8) ◽  
pp. 186 ◽  
Author(s):  
Urmi Das ◽  
Mohammad Salim Hossain
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Microcrystalline Cellulose ◽  
Matrix Tablets ◽  
Dissolution Time ◽  
Release Mechanism ◽  
Matrix Tablet ◽  
Weight Variation ◽  
The Matrix ◽  
Tablet Formulations

<p>Sustained release Carvedilol matrix tablets constituting Kollidon SR were developed in this study in an attempt to investigate the effect of release modifiers on the release profile of Carvedilol from matrix. Three matrix tablet formulations were prepared by direct compression of Kollidon SR in combination with release modifier (HPMC and Microcrystalline Cellulose) and magnesium stearate. Tablets containing only Kollidon SR with the active ingredient demonstrated a rapid rate of drug release. Incorporation of HPMC in the matrix tablet prolonged the release of drug but incorporation of Microcrystalline Cellulose showed superimposable release pattern with an initial burst effect as confirmed by mean dissolution time and Higuchi release rate data. After 7 hours of dissolution, Carvedilol release from the matrix systems were 91.42%, 83.41%, from formulation F1 and F2 respectively. Formulation F3 exhibited 100 % release at 4 hours. All the tablet formulations showed acceptable pharmaco-technical properties and complied with the in-house specifications for tablet weight variation, friability, hardness, thickness, and diameter. Prepared tablets also showed sustained release property for carvedilol. The drug release mechanism from the matrix tablets of F1 and F2 was found to be followed by Fickian and F3 by Non-Fickian mechanism.</p><p>DOI: <a href="http://dx.doi.org/10.3329/icpj.v1i8.11095">http://dx.doi.org/10.3329/icpj.v1i8.11095</a></p> <p>International Current Pharmaceutical Journal 2012, 1(8): 186-192</p>

scholarly journals The Effect of Manufacturing Methods and Different Shapes on the Release Pattern of Diclofenac Sodium Matrix Tablet

1970 ◽  
Vol 2 (2) ◽  
pp. 76-80
Author(s):  
Tajnin Ahmed ◽  
Muhammad Shahidul Islam ◽  
Tasnuva Haque ◽  
Mohammad Abusyed
Keyword(s):  
Sustained Release ◽  
Release Rate ◽  
Diclofenac Sodium ◽  
Matrix Tablets ◽  
Wet Granulation ◽  
Matrix Tablet ◽  
Direct Compression ◽  
Compression Method ◽  
Release Pattern ◽  
Peg 600

In the present study sustained release diclofenac sodium matrix tablets were prepared using Kollidon SR polymer. Hydroxypropyl methylcellulose (HPMC 15 cps) and poly ethylene glycol (PEG-600) polymers respectively were used in formulating tablets prepared by direct compression and wet granulation methods. The polymers were used to explore the release pattern of the drug into the dissolution media. The tablets were also prepared in various shapes (caplet oval, round oval and flat oval). A comparatively higher release rate of drug was obtained from the polymer HPMC 15 cps at 10% concentration for directly compressed matrix tablet than those containing 20% of HPMC after a definite period of time. In wet granulation process, 10% PEG-600 containing tablets showed a better release than those containing 20% PEG. The drug release was also found to be sustained in case of wet granulation method than that of the direct compression method. Again the caplet shaped tablets in case of direct compression method showed better release rate of drug than those of the round oval and flat oval shaped tablets. Thus the result of this study shows that the proper selection of the percentage of polymer and the suitable shape of tablet and proper manufacturing method can provide a greater opportunity in designing sustained release dosage forms. Key words: Matrix tablet; release pattern; direct compression; wet granulation; PEG 600; Kollidon SR.DOI: 10.3329/sjps.v2i2.5828Stamford Journal of Pharmaceutical Sciences Vol.2(2) 2009: 76-80

scholarly journals FORMULATION AND EVALUATION OF SUSTAINED RELEASE MATRIX TABLET OF LORNOXICAM BY DIRECT COMPRESSION METHOD

2021 ◽  
Vol 10 (5) ◽  
pp. 131-136
Author(s):  
Asim pasha ◽  
C N Somashekhar
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Matrix Tablets ◽  
In Vitro Dissolution ◽  
Prolonged Release ◽  
Matrix Tablet ◽  
Direct Compression ◽  
Dissolution Profile ◽  
Drug Content

The aim of the present work was to develop sustained release Lornoxicam matrix tablets with polymers like HPMC K15M, Ethyl cellulose, and Crospovidone as carriers in varying quantities. Direct compression was used to make matrix tablets. Various assessment parameters, such as hardness, friability, thickness, percent drug content, weight variation, and so on, were applied to the prepared formulations. In vitro dissolution studies were carried out for 24 hrs. The tablets were subjected to in-vitro drug release in (pH 1.2) for first 2 hrs. Then followed by (pH 6.8) phosphate buffer for next 22 hrs. And the results showed that among the six formulations FL3 showed good dissolution profile to control the drug release respectively. The drug and polymer compatibility were tested using FT-IR spectroscopy, which revealed that the drug was compatible with all polymers. It is also required to design an appropriate prolonged release formulation for Lornoxicam in order to maintain the drug's release. Hence by using the compatible polymers sustained release tablets were formulated and subjected for various types of evaluation parameters like friability, hardness, drug content and dissolution behaviour. Finally, the findings reveal that the prepared sustained release matrix tablets of lornoxicam have improved efficacy and patient compliance.

scholarly journals A REVIEW ON DISINTEGRATION CONTROL MATRIX TABLETS

2018 ◽  
Vol 8 (5) ◽  
pp. 19-22
Author(s):  
Pralhad K. Kanke ◽  
Pankaj Sawant ◽  
Ajit Jadhav ◽  
Md. Rageeb Md. Usman
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Solid Dispersion ◽  
Gastrointestinal Transit ◽  
Matrix Tablets ◽  
Surface Erosion ◽  
Matrix Tablet ◽  
Control Matrix ◽  
Dispersion Technique ◽  
Wax Coating

A number of sustained release formulations are available in the market which successfully sustained the drug release over a prolonged period of time by different mechanisms. The new approach for sustaining the drug release is disintegration control matrix tablet which sustained the drug release up to 24hrs by controlling the disintegration rate of tablet. Disintegration control matrix tablet (DCMT) mainly forms the granules containing drug and disintegrating agent such as low substituted hydroxyl propyl cellulose by various methods such as solid dispersion technique. The sustained release of drug is maintained by increasing the wax coating or decreasing the amount of disintegrants. The release of drug from tablet is uniform throughout till all the drug releases from tablet as it involves drug release by diffusion, dissolution and surface erosion mechanism. DCMT increases the solubility of drug and improves the bioavailability without disturbing gastrointestinal transit. BCS Class II, III, IV drugs are the best candidate for DCMT formulations. Keywords: Disintegration control matrix tablet (DCMT), Wax, Disintegrating agent, Solid dispersion.

scholarly journals A study on the influence of the formulation factors on in vitro release of ketoprofen from sustained release tablets

2021 ◽  
Vol 14 (1) ◽  
pp. 41-48
Author(s):  
Larisa Cimpoaie ◽  
◽  
Luca Liviu Rus ◽  
Rareș Iuliu Iovanov ◽  
◽  
...  
Keyword(s):  
Sustained Release ◽  
In Vitro Release ◽  
Matrix Tablets ◽  
Inert Matrix ◽  
Sustained Release Tablets ◽  
Formulation Factors ◽  
Release Data ◽  
Vitro Release ◽  
Inert Matrix Tablets

Objectives. The aim of this study was to investigate the influence of formulation factors on in vitro release of ketoprofen from sustained release inert matrix tablets. Materials and methods. Laboratory scale, Ketoprofen sustained release inert matrix tablets were manufactured using Kollidon® SR as matrix formator, by direct tableting of powder blends. The influence of the formulation factors (X1 – matrix formator excipient and X2 – diluent type) on in vitro release of ketoprofen from sustained release tablets was studied by using a full factorial 23 experimental plan. Outcomes. Pharmacotechnical characterization of manufactured laboratory scale batches was performed and all 12 batches fulfilled European Pharmacopeia requests. In vitro release showed a sustained release profile in all cases. Variance analysis (ANOVA) showed a good correlation between experimental conditions and answers. In vitro release testing was performed in phosphate buffer pH = 7.4. Percentage release was determined spectrophotometrically at 258 nm. A decrease in the rate of in vitro release was registered, up to 4 h and 6 h when lactose DC and mannitol DC were used as diluents, respectively. Isomalt DC has increased the rate of in vitro release up to 6 h. Conclusions. In vitro release data, corresponding to formulation N1 shoed a good fitting with Weitbull, Korshmeyer-Peppas and Higuchi models while in vitro release data corresponding to formulation N8 presented a good fitting with Weitbull and Korsmeyer-Peppas. In case of formulations N1 and N8 a non-Fickian diff usion mechanism seems to be involved in drug release from the matrix tablets.

scholarly journals Development and evaluation of sustained release losartan potassium matrix tablet using kollidon SR as release retardant

2012 ◽  
Vol 48 (4) ◽  
pp. 621-628 ◽  
Author(s):  
Shahid Sarwar ◽  
Mohammad Salim Hossain
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Release Kinetics ◽  
Polymer Concentration ◽  
In Vitro Release ◽  
Matrix Tablets ◽  
Losartan Potassium ◽  
Dissolution Time ◽  
Release Mechanism ◽  
Matrix Tablet

The present study was undertaken to develop sustained release (SR) matrix tablets of losartan potassium, an angiotensin-II antagonist for the treatment of hypertension. The tablets were prepared by direct compression method, along with Kollidon SR as release retardant polymer. The amount of losartan potassium remains fixed (100 mg) for all the three formulations whereas the amounts of Kollidon SR were 250 mg, 225 mg, and 200 mg for F-1, F-2, and F-3 respectively. The evaluation involves three stages: the micromeritic properties evaluation of granules, physical property studies of tablets, and in-vitro release kinetics studies. The USP apparatus type II was selected to perform the dissolution test, and the dissolution medium was 900 mL phosphate buffer pH 6.8. The test was carried out at 75 rpm, and the temperature was maintained at 37 ºC ± 0.5 ºC. The release kinetics was analyzed using several kinetics models. Higher polymeric content in the matrix decreased the release rate of drug. At lower polymeric level, the rate and extent of drug release were enhanced. All the formulations followed Higuchi release kinetics where the Regression co-efficient (R²) values are 0.958, 0.944, and 0.920 for F-1, F-2, and F-3 respectively, and they exhibited diffusion dominated drug release. Statistically significant (P<0.05) differences were found among the drug release profile from different level of polymeric matrices. The release mechanism changed from non-fickian (n=0.489 for F-1) to fickian (n=0.439 and 0.429 for F-2, and F-3 respectively) as a function of decreasing the polymer concentration. The Mean Dissolution Time (MDT) values were increased with the increase in polymer concentration.

scholarly journals Response Surface Optimization of Sustained Release Metformin-Hydrochloride Matrix Tablets: Influence of Some Hydrophillic Polymers on the Release

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Amitava Roy ◽  
Kalpana Roy ◽  
Sarbani Roy ◽  
Jyotirmoy Deb ◽  
Amitava Ghosh ◽  
...  
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Hydroxypropyl Methylcellulose ◽  
Dissolution Kinetics ◽  
Matrix Tablets ◽  
Metformin Hydrochloride ◽  
Wet Granulation ◽  
Matrix Tablet ◽  
Response Surface Optimization

The aim of the present work was designed to develop a model-sustained release matrix tablet formulation for Metformin hydrochloride using wet granulation technique. In the present study the formulation design was employed to statistically optimize different parameters of Metformin hydrochloride tablets at different drug-to-polymer ratios employing polymers Hydroxypropyl methylcellulose of two grades K4M and K100M as two independent variables whereas the dependent variables studied were X60, X120, T50, T90, n, and b values obtained from dissolution kinetics data. The in vitro drug release studies were carried out at simulated intestinal fluids, and the release showed a non-Fickian anomalous transport mechanism. The drug release was found to reveal zero order kinetics. The granules and the tablets were tested for their normal physical, morphological, and analytical parameters and were found to be within the satisfactory levels. There were no significant drug-polymer interactions as revealed by infrared spectra. It has been found out that on an optimum increased Hydroxypropyl methylcellulose K100M concentration and decreased Hydroxypropyl methylcellulose K4M concentration the formulations were elegant in terms of their release profiles and were found to be statistically significant and generable.

scholarly journals Formulation and Evaluation of Sustained Release Matrix Tablet of Itopride

2021 ◽  
Vol 11 (5) ◽  
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Ethyl Cellulose ◽  
Chemical Interaction ◽  
Research Work ◽  
Matrix Tablets ◽  
Crystalline Cellulose ◽  
Matrix Tablet ◽  
Natural Polymers ◽  
Drug Release Profile

The objective of this research work was to carry out design and evaluation of sustained release matrix tablets of Itopride by use of natural and synthetic polymers. Matrix tablets were prepared by wet granulation technique by using natural polymers like Carbopol 934, Tamarind poly saccharide, Locust bean gum, Ethyl cellulose, HPMC K 100 as matrix forming agent and excipients such as Lactose, Starch 1500, Magnesium stearate, MCC and talc were used. The dissolution medium consisted of 900 ml of 0.1 N HCl for first 2 hours and then 7.4 phosphate buffer for remaining 10 hours. The release of Itopride from matrix containing lactose, micro crystalline cellulose and starch 1500 as diluents. The drug release rate was found in order of lactose> micro crystalline cellulose>starch 1500. The formulation was optimized on the basis of acceptable tablet properties and in-vitro drug release. The release data were fit into different kinetic models (zero-order, first- order, Higuchi’s equation and Korsmeyer-Peppas equation). Optimized formulation was tested for their compatibility with Itopride by FT-IR studies, which revealed that there is no chemical interaction occurred with polymer and other excipients. The drug release profile of the best formulation was well controlled and uniform throughout the dissolution studies. Keywords: Matrix tablets, Itopride, Carbopol 934, HPMC K 100, Ethyl cellulose.

scholarly journals Formulation and Evaluation of Gabapentin Sustained Release Matrix Tablet Using Hibiscus rosa sinensis Leaves Mucilage as Release Retardant

2021 ◽  
pp. 564-572
Author(s):  
P. Amsa ◽  
G. K. Mathan ◽  
S. Magibalan ◽  
E. K. Velliyangiri ◽  
T. Kalaivani ◽  
...  
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Magnesium Stearate ◽  
Matrix Tablets ◽  
Wet Granulation ◽  
Matrix Tablet ◽  
Hibiscus Rosa Sinensis

The major goal of this study was to develop and evaluate Sustained release matrix tablets of Gabapentin with Hibiscus rosa - sinensis leaves mucilage prepared by using wet granulation technique with microcrystalline cellulose as a diluents and magnesium stearate as a lubricant. Pre-compression and post-compression evaluation of physicochemical parameters were carried out and to be within acceptable limits. Drug and polymer compatibility were validated by FTIR measurements. Further, tablets were evaluated for in vitro release study. To get the sustained release of Gabapentin, the concentration of Hibiscus rosa- sinensis mucilage was tuned with a gas-generating agent. The % drug release of all formulation from F1 to F5 showed 91.24%, 80.24%, 70.53%, 62.12% and 49.83% respectively. All the dosage form release kinetics was computed using zero order, first order, Higuchi, and Korsmeyer–Peppas methods. From the above results, it is concluded that the n value of formulation F5 showed 0.78 suggesting anomalous (non-fickian) behavior of the drug. Mucilage from the leaves of Hibiscus rosa-sinensis has a great retarding effect in drug release from sustained release tablets.

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