Hot Melt Coating: Development and Optimization of Controlled Release Formulation and Process of Oxcarbazepine

Hot-melt coating process (HMCP) is being developed to formulate lipid based oral controlled release formulation system for anti-epileptic drug Oxcarbazepine. Pellets containing Active ingredient in the core portion were prepared by extrusion spheronization process with use of appropriate filler and binder. These core pellets were then coated using hot-melt coating technology with different levels of solid lipid material and a hydrophilic component. Formulation and Process parameters were optimized to achieve targeted drug release profile and other target product profile with particular focus on HMCP. Quality by design (QbD) with DOE approach was used for designing and development of the formulation, by putting risk assessment (FMEA, Fish-bone diagram), screening (by Plackett Burman), and optimization (by CCC) studies. Appropriate ‘design space’ was proposed based on the optimization studies. The results demonstrated that the level of Low melting coating component and a hydrophilic component influenced the drug release rate from the formulation, and the rate of release could be optimized by varying the amount of these components in the formulation. Processing parameters like Temperature of the coating solution and atomization air, Atomization air pressure and Spray rate also affects the drug release rate and other parameters like coating efficiency and mean particle size. For optimized formulation, dissolution data model fitting was also carried out which adequately fits to Higuchi model suggesting that the drug release occurred predominantly by diffusion.

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Development and Optimization of Controlled Release Formulation and Process of Levetiracetam with Hot Melt Coating Technology

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i26b31485 ◽

2021 ◽

pp. 80-102

Author(s):

Nilam Patel ◽

Rupal Jani

Keyword(s):

Controlled Release ◽

Drug Release ◽

Release Rate ◽

Water Soluble ◽

Coating Process ◽

Drug Release Rate ◽

Release Formulation ◽

Coating Technology ◽

Controlled Release Formulation ◽

Hot Melt

Conventional coating processes are based on aqueous or organic solvent system, resulting in the lengthy and tedious processes where use and removal of solvents consumes lots of energy and resources. Also, solvent disposal is a critical issue considering environmental hazard.Hot melt coating process avoids use of solvent and is short and energy-efficient process. Here, Hot-melt coating process (HMCP) is being developed to formulate lipid based oral controlled release formulation system to deliver highly water soluble Biopharmaceutical Classification System (BCS) class-I drug Levetiracetam. Pellets containing Active ingredient in the core portion were prepared by extrusion spheronization process with use of appropriate filler and binder. These core pellets were then coated using hot-melt coating technology with different levels of lipid and a hydrophilic component. Formulation and Process parameters were optimized to achieve targeted drug release profile and other target product profile with particular focus onHMCP. Quality by design (QbD) with DOE approach was used for designing and development of the formulation, by putting risk assessment Failure Mode and Effect analysis (FMEA, Fish-bone diagram), screening (by Plackett Burman), and optimization by Central Composite Design (CCC) studies. Appropriate ‘design space’ was proposed based on the optimization studies. The results demonstrated that the level of Low melting coating component and a hydrophilic component influenced the drug release rate from the formulation, and the rate of release could be optimized by varying the amount of these components in the formulation. Processing parameters like Temperature of the coating solution and atomization air, Atomization air pressure and Spray rate also affects the drug release rate and other parameters like coating efficiency and mean particle size. For optimized formulation, dissolution data model fitting was also carried out which adequately fits to Higuchi model suggesting that the drug release occurred predominantly by diffusion.

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Development and evaluation of in situ novel intragastric controlled-release formulation of hydrochlorothiazide

Acta Pharmaceutica ◽

10.2478/v10007-011-003-9 ◽

2011 ◽

Vol 61 (1) ◽

pp. 73-82 ◽

Cited By ~ 4

Author(s):

Ravikumar Patel ◽

Jayvadan Patel

Keyword(s):

Controlled Release ◽

Drug Release ◽

New Technology ◽

Release Mechanism ◽

Drug Release Profile ◽

Release Formulation ◽

Controlled Release Formulation ◽

Rigid Mass ◽

Formulation Factors

Development and evaluation of in situ novel intragastric controlled-release formulation of hydrochlorothiazide In situ forming intragastric controlled-release formulation is a new technology in the field of oral controlled-release delivery systems. The objective of this study was to develop formulations that can control drug release up to 24 hours. In addition, a combination of appropriate polymers and solvents was selected that could form a drug loaded gel at the process temperature of 60-70 °C, which gel could turn into a rigid mass upon exposure to dissolution fluid at body temperature. The drug release mechanism from this rigid mass was controlled by different formulation factors such as different polymer grades, polymer concentrations, hydrophobicity or hydrophilicity of solvents, different drug loadings, and physicochemical properties of additional excipients. After evaluating different formulation factors, Ethocel 10 FP and triethyl citrate were selected for further studies using hydrochlorothiazide as a model drug. Polynomial correlation between viscosity of the blank gel and drug release profile was also obtained.

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Optimization Study to Develop Once-a-day Controlled Release Formulation of Metoclopramide with Predictable Design Space

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/10.37285/ijpsn.2008.1.1.6 ◽

1970 ◽

Vol 1 (1) ◽

pp. 71-76

Author(s):

Rajesh Dubey ◽

Udaya K. Chowdary ◽

Venkateswarlu V.

Keyword(s):

Controlled Release ◽

Drug Release ◽

Design Space ◽

Release Kinetics ◽

Release Profile ◽

Release Formulation ◽

Linear Effect ◽

Controlled Release Formulation ◽

The Difference ◽

Face Centered

A controlled release formulation of metoclopramide was developed using a combination of hypromellose (HPMC) and hydrogenated castor oil (HCO). Developed formulations released the drug over 20 hr with release kinetics following Higuchi model. Compared to HCO, HPMC showed significantly higher influence in controlling the drug release at initial as well as later phase. The difference in the influence can be explained by the different swelling and erosion behaviour of the polymers. Effect of the polymers on release was optimized using a face-centered central composite design to generate a predictable design space. Statistical analysis of the drug release at various levels indicated a linear effect of the polymers’ levels on the drug release. The release profile of formulations containing the polymer levels at extremes of their ranges in design space was found to be similar to the predicted release profile

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Microorganism-based monodisperse microcapsules: encapsulation of the fungicide tebuconazole and its controlled release properties

RSC Advances ◽

10.1039/c5ra01629k ◽

2015 ◽

Vol 5 (32) ◽

pp. 25164-25170 ◽

Cited By ~ 6

Author(s):

Bo Zhang ◽

Teng Zhang ◽

Quanxi Wang ◽

Tianrui Ren

Keyword(s):

Controlled Release ◽

Powdery Mildew ◽

Drug Release ◽

Release Rate ◽

Drug Release Rate ◽

Burst Effect ◽

Initial Burst ◽

Release System ◽

Controlled Release System ◽

Monodisperse Microcapsules

A controlled release system was prepared, it based on UF modified PCC cells in which TEB are loaded into cells. It can control the drug release rate, depress the initial “burst effect”, and was efficacious in controlling wheat powdery mildew.

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Drug Release from a Spherical Matrix: Theoretical Analysis for a Finite Dissolution Rate Affected by Geometric Shape of Dispersed Drugs

Pharmaceutics ◽

10.3390/pharmaceutics12060582 ◽

2020 ◽

Vol 12 (6) ◽

pp. 582

Author(s):

Yung-Sheng Lin ◽

Ruey-Yug Tsay

Keyword(s):

Drug Release ◽

Release Rate ◽

Shape Factor ◽

Numerical Solutions ◽

Drug Loading ◽

Spherical Geometry ◽

Detailed Comparison ◽

Release Profile ◽

Drug Release Profile ◽

Drug Release Rate

Amending the neglect of finite dissolution in traditional release models, this study proposed a more generalized drug release model considering the simultaneous dissolution and diffusion procedure from a drug-loaded spherical matrix. How the shape factor (n = 0, 1/2, and 2/3 for the planar, cylindrical, and spherical geometry, respectively) of dispersed drug particles affected the release from the matrix was examined for the first time. Numerical solutions of this generalized model were validated by consensus with a short-time analytical solution for planar drugs and by the approach of the diffusion-controlled limits with Higuchi’s model. The drug release rate increases with the ratio of dissolution/diffusion rate (G) and the ratio of solubility/drug loading (K) but decreases with the shape factor of drug particles. A zero-order release profile is identified for planar drugs before starting the surface depletion layer, and also found for cylindrical and spherical dispersed drugs when K and G are small, i.e. the loaded drug is mainly un-dissolved and the drug release rate is dissolution-controlled. It is also shown that for the case of a small G value, the variation of drug release profile, due to the drug particle geometry, becomes prominent. Detailed comparison with the results of the traditional Higuchi’s model indicates that Higuchi’s model can be applied only when G is large because of the assumption of an instantaneous dissolution. For K = 1/101–1/2, the present analysis suggests an error of 33–85% for drug release predicted by Higuchi’s model for G = 100, 14–44% error for G = 101, while a less than 5% error for G ≧ 103.

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The effect of molecular structure on the anticancer drug release rate from prodrug nanoparticles

Chemical Communications ◽

10.1039/c5cc04164c ◽

2015 ◽

Vol 51 (64) ◽

pp. 12835-12838 ◽

Cited By ~ 17

Author(s):

Yoshikazu Ikuta ◽

Yoshitaka Koseki ◽

Tsunenobu Onodera ◽

Hidetoshi Oikawa ◽

Hitoshi Kasai

Keyword(s):

Molecular Structure ◽

Controlled Release ◽

Drug Release ◽

Anticancer Drug ◽

Release Rate ◽

Chemical Structure ◽

Anticancer Agent ◽

Drug Release Rate ◽

Drug Nanoparticles

The controlled release of an anticancer agent from drug nanoparticles could be successfully achieved by optimizing the chemical structure of dimeric compounds as prodrug.

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Development and evaluation of verapamil resinates-loaded controlled release microcapsules using a binary polymer system in drug release rate modulation

Bulletin of Pharmaceutical Sciences. Assiut ◽

10.21608/bfsa.2001.65906 ◽

2001 ◽

Vol 24 (2) ◽

pp. 115-134

Author(s):

I. El-Gibaly ◽

M. Fathy

Keyword(s):

Controlled Release ◽

Drug Release ◽

Release Rate ◽

Polymer System ◽

Drug Release Rate ◽

Rate Modulation ◽

Binary Polymer

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Preparation of Liquid Oral Mucoadhesive Gastro-retentive System of Nimodipine

Current Drug Delivery ◽

10.2174/1567201816666191014102531 ◽

2019 ◽

Vol 16 (9) ◽

pp. 862-871 ◽

Cited By ~ 3

Author(s):

Mai Mamdouh ◽

Ahmed Donia ◽

Ebtessam Essa ◽

Gamal El Maghraby

Keyword(s):

Critical Care ◽

Controlled Release ◽

Drug Release ◽

Release Rate ◽

Poloxamer 407 ◽

Liquid Form ◽

Drug Release Rate ◽

Alginate Concentration ◽

Gastro Retentive

Background: Nimodipine is a calcium channel blocker frequently used in critical care settings. It is mainly absorbed in the upper gastrointestinal tract. Accordingly, the development of gastroretentive formulation will be beneficial. The benefit would be maximized for critical care patients if the developed system was in liquid form to facilitate the administration through nasogastric tubing. Objective: Development of gastro-retentive liquid oral controlled release formulation of nimodipine through in situ gellation. Methods: Nimodipine dissolution was improved by solid dispersion (SD) using poloxamer 407. Sodium alginate solutions (1, 1.5 and 2%w/v) were loaded with the optimized SD microparticles. Carboxymethylcellulose was added to modulate the release and to augment mucoadhesion power. All in situ gelling alginate solutions were characterized regarding viscosity, gelling capacity and drug release. SD microparticles showed considerable improvement in nimodipine dissolution. Results: All alginate systems were pourable. Increasing alginate concentration increased the gelling capacity and reduced drug release rate. The addition of carboxymethylcellulose produced greater control over drug release rate. X-ray radiography showed successful stomach-retention over 8 hours in rabbits, which correlates with the controlled release pattern of the developed systems. Conclusion: The study provides the formulator with a range of gastroretentive controlled release formulations of nimodipine while maintaining the convenience of administration through nasogastric tubing with the potential for enhanced bioavailability.

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Lipid-Based Implants: Impact of Formulation Parameters

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.1060.87 ◽

2014 ◽

Vol 1060 ◽

pp. 87-90

Author(s):

Marisa Nicolai ◽

Vanessa Amaral ◽

Cátia Antunes ◽

Duangratana Shuwisitkul ◽

Joana Portugal Mota

Keyword(s):

Controlled Release ◽

Drug Release ◽

Release Rate ◽

Release Rates ◽

Drug Release Rate ◽

Blend Ratio ◽

Drug Type ◽

Formulation Parameters ◽

Blend Ratios ◽

Aqueous Solubilities

Lipid implants have been attracting attention in recent years. However, to better understand these systems, more fundamental studies are required. The objective of this work was to evaluate the effect of some formulation parameters, namely lipid and drug type, implant shape/surface area and lipid blend ratio, on drug release rate. The developed implants were cylindrical or spherical in shape with an even surface. Caffeine release from glycerol-trimyristate implant was very fast when compared with glycerol-tristerate matrix. The latter allowed a 4 month controlled release in contrast with glycerol-trimyristate matrix (~ 5 days). Caffeine and theophylline presented similar release rates, despite their different aqueous solubilities. In addition, different lipid blend ratios provided different release profiles for caffeine.

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