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.

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.

3 (2) Factorial Design Assisted Crushed Puffed Rice-HPMC-Chitosan based Hydrodynamically Balanced System of Metoprolol Succinate

2020 ◽  
Vol 10 (3) ◽  
pp. 237-249
Author(s):  
Shashank Soni ◽  
Veerma Ram ◽  
Anurag Verma
Keyword(s):  
Drug Release ◽  
Factorial Design ◽  
Hydroxypropyl Methylcellulose ◽  
Batch Size ◽  
Metoprolol Succinate ◽  
Zero Order Kinetics ◽  
Two Factors ◽  
Puffed Rice ◽  
Model Drug

Introduction: Hydrodynamically balanced system (HBS) possesses prolonged and continuous delivery of the drug to the gastrointestinal tract which improves the rate and extent of medications that have a narrow absorption window. The objective of this work was to develop a Hydrodynamically Balanced System (HBS) of Metoprolol Succinate (MS) as a model drug for sustained stomach specific delivery. Materials and Methods: Experimental batches were designed according to 3(2) Taguchi factorial design. A total of 9 batches were prepared for batch size 100 capsules each. Formulations were prepared by physically blending MS with polymers followed by encapsulation into hard gelatin capsule shell of size 0. Polymers used were Low Molecular Weight Chitosan (LMWCH), Crushed Puffed Rice (CPR), and Hydroxypropyl Methylcellulose K15 M (HPMC K15M). Two factors used were buoyancy time (Y1) and time taken for 60% drug release (T60%; Y2). Results: The drug excipient interaction studies were performed by the thermal analysis method which depicts that no drug excipient interaction occurs. In vitro buoyancy studies and drug release studies revealed the efficacy of HBS to remain gastro retentive for a prolonged period and concurrently sustained the release of MS in highly acidic medium. All formulations followed zero-order kinetics. Conclusion: Developed HBS of MS with hydrogel-forming polymers could be an ideal delivery system for sustained stomach specific delivery and would be useful for the cardiac patients where the prolonged therapeutic action is required.

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 Automatic Dissolution Testing with High-Temporal Resolution for Both Immediate-Release and Fixed-Combination Drug Tablets

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Zhongmei Chi ◽  
Irfan Azhar ◽  
Habib Khan ◽  
Li Yang ◽  
Yunxiang Feng
Keyword(s):  
High Speed ◽  
Sequential Analysis ◽  
Immediate Release ◽  
Drug Dissolution ◽  
High Temporal Resolution ◽  
Dissolution Profile ◽  
Dissolution Testing ◽  
Combination Drug ◽  
Efficient Separation ◽  
High Efficient

AbstractDissolution testing plays many important roles throughout the pharmaceutical industry, from the research and development of drug products to the control and evaluation of drug quality. However, it is a challenging task to perform both high-efficient separation and high-temporal detection to achieve accurate dissolution profile of each active ingredient dissolved from a drug tablet. In our study, we report a novel non-manual-operation method for performing the automatic dissolution testing of drug tablets, by combining a program-controlled sequential analysis and high-speed capillary electrophoresis for efficient separation of active ingredients. The feasibility of the method for dissolution testing of real drug tablets as well as the performance of the proposed system has been demonstrated. The accuracy of drug dissolution testing is ensured by the excellent repeatability of the sequential analysis, as well as the similarity of the evaluation of dissolution testing. Our study show that the proposed method is capable to achieve simultaneous dissolution testing of multiple ingredients, and the matrix interferences can be avoided. Therefore it is of potential valuable applications in various fields of pharmaceutical research and drug regulation.

Evaluation of Parts Produced by a Novel Additive Manufacturing Process

2013 ◽  
Vol 315 ◽  
pp. 63-67 ◽  
Author(s):  
Muhammad Fahad ◽  
Neil Hopkinson
Keyword(s):  
Additive Manufacturing ◽  
Rapid Prototyping ◽  
Manufacturing Process ◽  
High Speed ◽  
Three Dimensional ◽  
Coordinate Measuring Machine ◽  
Layer By Layer ◽  
Nylon 12 ◽  
Measuring Machine ◽  
End Use

Rapid prototyping refers to building three dimensional parts in a tool-less, layer by layer manner using the CAD geometry of the part. Additive Manufacturing (AM) is the name given to the application of rapid prototyping technologies to produce functional, end use items. Since AM is relatively new area of manufacturing processes, various processes are being developed and analyzed for their performance (mainly speed and accuracy). This paper deals with the design of a new benchmark part to analyze the flatness of parts produced on High Speed Sintering (HSS) which is a novel Additive Manufacturing process and is currently being developed at Loughborough University. The designed benchmark part comprised of various features such as cubes, holes, cylinders, spheres and cones on a flat base and the build material used for these parts was nylon 12 powder. Flatness and curvature of the base of these parts were measured using a coordinate measuring machine (CMM) and the results are discussed in relation to the operating parameters of the process.The result show changes in the flatness of part with the depth of part in the bed which is attributed to the thermal gradient within the build envelope during build.

Physicochemical Evaluation of Brands of Amlodipine Besylate Tablets.

2020 ◽  
Vol 1 (5) ◽  
pp. 24-33
Author(s):  
C.A. Anyanwu-Ndulewe ◽  
◽  
L.E. Mogbolu ◽  
M.A. Oladunni ◽  
A.A. Adepoju-Bello
Keyword(s):  
Hardness Test ◽  
Drug Market ◽  
The United States ◽  
Financial Strain ◽  
Average Weight ◽  
Dissolution Profile ◽  
Amlodipine Besylate ◽  
Disintegration Time ◽  
Physicochemical Evaluation ◽  
Dissolution Efficiency

Background: Hypertension is a chronic condition, and the cost of filling prescriptions has a potential of putting a financial strain on patients, hence the need for lower priced but bioequivalent generics. The Nigerian drug market is awash with generics of Amlodipine besylate, a first line drug in the treatment of hypertension, therefore, any prescribed alternative must be bioequivalent to the originator. Objectives: This study assessed the physicochemical properties of some brands in order to predict pharmaceutical and bioequivalence and invariably, the interchangeability with the innovator brand. Methods: Compendial parameters of average weight, friability, disintegration, drug content and dissolution profile of ten generic brands were evaluated using the United States Pharmacopeia (USP) as well as the non-official hardness test. Results: Two brands failed the test for hardness, while still keeping to the stipulated friability limit. All the brands met the required disintegration time, irrespective of the discordance of some brands in the breaking force and friability values. All brands were found to contain between 92.00 and 103.57% (w/w) of Amlodipine besylate. Two brands failed to achieve ≥75% dissolution expected at 30 minutes and this was reflected in the low f2 values of 35.06% and 28.73%. The dissolution curves displayed a similarity for two brands, which was also corroborated by the high percentage dissolution efficiency (DE) of 92.00%, as well as the f1 and f2 values, compared to the innovator brand. Conclusion: Although the parameters used may predict therapeutic equivalence, interchangeability with the comparator brand is subject to relevant bioequivalence studies.

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