Gastroretentive bilayer film for sustained release of atorvastatin calcium and immediate release of amlodipine besylate: pharmaceutical, pharmacokinetic evaluation, and IVIVC

2019 ◽  
Vol 25 (4) ◽  
pp. 416-431 ◽  
Author(s):  
Amit Porwal ◽  
Harinath Dwivedi ◽  
Kamla Pathak
Keyword(s):  
Sustained Release ◽  
Immediate Release ◽  
Bilayer Film ◽  
Amlodipine Besylate ◽  
Atorvastatin Calcium ◽  
Pharmacokinetic Evaluation

scholarly journals Development of a Scalable Process of Film-Coated bi-Layer Tablet Containing Sustained-Release Metoprolol Succinate and Immediate-Release Amlodipine Besylate

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1797
Author(s):  
Nguyen Thi Linh Tuyen ◽  
Le Quan Nghiem ◽  
Nguyen Duc Tuan ◽  
Phuoc Huu Le
Keyword(s):  
Sustained Release ◽  
Manufacturing Process ◽  
High Speed ◽  
Immediate Release ◽  
New Drugs ◽  
Batch Size ◽  
Average Weight ◽  
Amlodipine Besylate ◽  
Metoprolol Succinate ◽  
Dry Mixing

The development of new drugs that combine active ingredients for the treatment hypertension is critically essential owing to its offering advantages for both patients and manufacturers. In this study, for the first time, detailed development of a scalable process of film-coated bi-layer tablets containing sustained-release metoprolol succinate and immediate-release amlodipine besylate in a batch size of 10,000 tablets is reported. The processing parameters of the manufacturing process during dry mixing-, drying-, dry mixing- completion stages were systematically investigated, and the evaluation of the film-coated bi-layer tablet properties was well established. The optimal preparation conditions for metoprolol succinate layer were 6 min- dry mixing with a high-speed mixer (120 rpm and 1400 rpm), 30-min drying with a fluid bed dryer, and 5-min- mixing completion at 25 rpm. For the preparation of amlodipine besylate layer, the optimal dry-mixing time using a cube mixer (25 rpm) was found to be 5 min. The average weight of metoprolol succinate layers and bi-layer tablets were controlled at 240–260 mg and 384–416 mg, respectively. Shewhart R chart and X¯ charts of all three sampling lots were satisfactory, confirming that the present scalable process was stable and successful. This study confirms that the manufacturing process is reproducible, robust; and it yields a consistent product that meets specifications.

scholarly journals FORMULATION AND INVESTIGATION OF POLYMERIC MULTIPLE UNIT PELLET SYSTEMS CONSISTING OF SUSTAINED RELEASE GLIMEPIRIDE AND IMMEDIATE RELEASE ATORVASTATIN CALCIUM

2019 ◽  
pp. 142-150
Author(s):  
BHARAT BIJAPUR ◽  
GOWDA DV ◽  
VISHAL GUPTA N ◽  
SHAILESH THIRUMALESHWAR ◽  
PRAVEEN SIVADASU ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Sustained Release ◽  
Immediate Release ◽  
Fixed Dose ◽  
Locust Bean Gum ◽  
Natural Polymers ◽  
Atorvastatin Calcium ◽  
Gum Ghatti ◽  
Multiple Unit ◽  
Locust Bean

Objective: The objective of the present work was to develop novel fixed-dose combinations (FDCs) for improvement of glucose tolerance in type II diabetes mellitus patients associated with dyslipidemia. Methods: Multiple unit pellet systems (MUPSs) consisting of sustained release (SR) glimepiride and immediate release atorvastatin calcium pellets were formulated. The SR glimepiride pellets were prepared using a combination of locust bean gum and gum ghatti/guar gum. Similarly, the immediate release of atorvastatin calcium pellets was prepared using locust bean gum suspension as a binder. Results: The formulated pellets were characterized using Fourier transform infrared spectroscopy (FTIR) and Differential scanning calorimetry (DSC). Further, surface morphology of the formulated pellets was done by scanning electron microscopy (SEM). FT-IR and DSC studies suggested that there were no chemical interactions between the drug and natural polymers. SEM studies revealed that formulated pellets were in spherical shape. Based on in vitro evaluation, the SR glimepiride formulation developed using a combination of 2% locust bean gum and 2.5% gum ghatti polymers sustained the release of the drug up to 12 h. Similarly, the immediate release atorvastatin calcium formulation containing 1% w/w locust bean gum suspension as a binder and 7% croscarmellose sodium showed fast disintegration of pellets. The in vivo studies in albino Wistar rat revealed that there was an improvement in bioavailability of the drugs. Stability studies showed that there were no significant changes in the drug content and physical appearance of the prepared SR glimepiride and immediate release atorvastatin pellet formulations. Conclusion: Thus, the formulated FDC as MUPS can be used as an alternative approach for treating diabetes mellitus-induced dyslipidemia.

scholarly journals FORMULATION OF IMMEDIATE RELEASE (IR) ATORVASTATIN CALCIUM PELLETS AND SUSTAINED RELEASE (SR) GLIBENCLAMIDE FOR FIXED-DOSE COMBINATION DOSAGE FORM

2018 ◽  
Vol 11 (12) ◽  
pp. 159
Author(s):  
Kowshik K ◽  
Vishal Gupta N ◽  
Gowda Dv ◽  
Praveen Sivadasu
Keyword(s):  
Sustained Release ◽  
Guar Gum ◽  
Immediate Release ◽  
Fixed Dose ◽  
Locust Bean Gum ◽  
Atorvastatin Calcium ◽  
Dsc Studies ◽  
Ft Ir ◽  
Locust Bean

Objective: The objective of the present research was to develop fixed-dose combinations for the treatment of dyslipidemia, associated with type-II diabetes mellitus for improvement of glucose tolerance.Methods: Multiple unit pellet systems (MUPSs) consisting immediate release atorvastatin calcium pellets and sustained release glibenclamide were formulated by spheronization technique. The characterization of formulated pellets was done by Fourier transform infrared (FT-IR) and differential scanning calorimetry (DSC) studies, and formulated pellets were evaluated for solubility, viscosity, pH, and in vitro studies.Results: From FT-IR and DSC studies, it was confirmed that no chemical interaction existed between the drug and the natural polymers used. Solubility of glibenclamide was found to be 4.38 and 18.24 and atorvastatin calcium was found to be 6.84, 214.67, and 287.43 g/L. The viscosity of 1% w/v of locust bean gum, guar gum, and ghatti gum was found to be 169 cP, 124 cP, and 31 cP in distilled water. The pH of locust bean gum, guar gum, and gum ghatti solutions was found to be 5.6±0.49, 5.2±0.27, and 4.7±0.51. The in vitro studies suggested that glibenclamide pellets had shown a sustained release till 12 h, while atorvastatin calcium had shown immediate release of drug due to rapid disintegration of pellets.Conclusion: Thus, MUPS can be considered as an alternative approach to treat diabetes induced dyslipidemia.

Formulation and Evaluation of Atorvastatin Calcium-Poly-ε-Caprolactone Nanoparticles Loaded Ocular Inserts for Sustained Release and Antiinflammatory Efficacy

2020 ◽  
Vol 21 (15) ◽  
pp. 1688-1698
Author(s):  
Germeen N.S. Girgis
Keyword(s):  
Sustained Release ◽  
In Vitro Release ◽  
Pluronic F127 ◽  
In Vivo Study ◽  
Average Weight ◽  
Drug Release Profile ◽  
Atorvastatin Calcium ◽  
Anti Inflammatory

Purpose: The work was performed to investigate the feasibility of preparing ocular inserts loaded with Poly-ε-Caprolactone (PCL) nanoparticles as a sustained ocular delivery system. Methods: First, Atorvastatin Calcium-Poly-ε-Caprolactone (ATC-PCL) nanoparticles were prepared and characterized. Then, the optimized nanoparticles were loaded within inserts formulated with Methylcellulose (MC) and Polyvinyl Alcohol (PVA) by a solvent casting technique and evaluated physically, for in-vitro drug release profile. Finally, an in-vivo study was performed on the selected formulation to prove non-irritability and sustained ocular anti-inflammatory efficacy compared with free drug-loaded ocuserts. Results: The results revealed (ATC-PCL) nanoparticles prepared with 0.5% pluronic F127 were optimized with 181.72±3.6 nm particle size, 0.12±0.02 (PDI) analysis, -27.4± 0.69 mV zeta potential and 62.41%±4.7% entrapment efficiency. Nanoparticles loaded ocuserts manifested compatibility between drug and formulation polymers. Moreover, formulations complied with average weight 0.055±0.002 to 0.143±0.023 mg, and accepted pH. ATC-PCL nanoparticles loaded inserts prepared by 5% MC showed more sustained, prolonged in-vitro release over 24h. In-vivo study emphasized non-irritability, ocular anti-inflammatory effectiveness represented by smaller lid closure scores, and statistically significant lowering in PMN count after 3h. Conclusion: These findings proposed a possibly simple, new and affordable price technique to prepare promising (ATC-PCL) nanoparticles loaded inserts to achieve sustained release with prolonged antiinflammatory efficacy.

scholarly journals Development and In Vitro-In Vivo Evaluation of a Novel Sustained-Release Loxoprofen Pellet with Double Coating Layer

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 260 ◽  
Author(s):  
Dongwei Wan ◽  
Min Zhao ◽  
Jingjing Zhang ◽  
Libiao Luan
Keyword(s):  
Citric Acid ◽  
Drug Release ◽  
Sustained Release ◽  
Release Rate ◽  
Diffusion Rate ◽  
Immediate Release ◽  
Pharmacokinetic Studies ◽  
Release Tablet

This study aimed to develop a novel sustained release pellet of loxoprofen sodium (LXP) by coating a dissolution-rate controlling sub-layer containing hydroxypropyl methyl cellulose (HPMC) and citric acid, and a second diffusion-rate controlling layer containing aqueous dispersion of ethyl cellulose (ADEC) on the surface of a LXP conventional pellet, and to compare its performance in vivo with an immediate release tablet (Loxinon®). A three-level, three-factor Box-Behnken design and the response surface model (RSM) were used to investigate and optimize the effects of the citric acid content in the sub-layer, the sub-layer coating level, and the outer ADEC coating level on the in vitro release profiles of LXP sustained release pellets. The pharmacokinetic studies of the optimal sustained release pellets were performed in fasted beagle dogs using an immediate release tablet as a reference. The results illustrated that both the citric acid (CA) and ADEC as the dissolution- and diffusion-rate controlling materials significantly decreased the drug release rate. The optimal formulation showed a pH-independent drug release in media at pH above 4.5 and a slightly slow release in acid medium. The pharmacokinetic studies revealed that a more stable and prolonged plasma drug concentration profile of the optimal pellets was achieved, with a relative bioavaibility of 87.16% compared with the conventional tablets. This article provided a novel concept of two-step control of the release rate of LXP, which showed a sustained release both in vitro and in vivo.

scholarly journals Formulation, Development and Evaluation of Bilayer Floating Tablet of Gemfibrozil

2019 ◽  
Vol 9 (4) ◽  
pp. 574-578
Author(s):  
Mohammad Faizan Mohammad Gufran ◽  
Sailesh Kumar Ghatuary ◽  
Reena Shende ◽  
Prabhat Kumar Jain ◽  
Geeta Parkhe
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Hydroxypropyl Methylcellulose ◽  
Immediate Release ◽  
In Vitro Dissolution ◽  
Log P ◽  
Physical Parameters ◽  
Direct Compression ◽  
Formulation Development ◽  
Compression Technique

Formulation development is an important part of drug design and development. Bioavailability and bioequivalence are totally dependent on formulation development. Now-a-days formulation development is done by following QbD (Quality by Design).The aim of present study is to formulate Gemfibrozil (Gem) sustained release (SR) and immediate release (IR) bilayer tablet by different concentration of Hydroxypropyl methylcellulose (HPMC) and HPMC K 100 M to control the release pattern. The sustained release layer of Gem was prepared by using different grades of HPMC like, HPMC K-15, HPMC K-4 along with other excipients by direct compression technique. The immediate release layer of Gem was prepared by Cross carmellose sodium, Crospovidone and Sodium starch glycolate by direct compression technique. The powders were evaluated for their flow properties and the finished tablets were evaluated for their physical parameters. The both immediate release and sustained release layers of Gem were characterized by FT-IR and in vitro dissolution studies. The drug release study of Gem was evaluated using USP-II paddle type dissolution apparatus. The release rate of Gem in immediate release layer was studied for 15 min in 0.1 N HCL media and that of Gem in sustained release layer was studied for 12 h in 0.1 N HCL. From the nine batches F6 batch showed good release behaviour 99.85% of drug is released over 12 hours. Gem belongs to BCS Class II (log P 3.6) with poor solubility and high permeability resulting in limited and variable bioavailability. Total four trial batches of each drug have been manufactured to optimize and develop a robust and stable formulation, the stability studies of the products also comply with ICH guideline. Keywords: Bilayer floating tablets, Gemfibrozil, Biphasic drug release, HPMC K 15.

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