The aim of the present studies was to develop and characterize 2.6 mg sustained release matrix tablets of Nitroglycerin. Tablets were prepared by direct compression method. Methocel K15M CR and Methocel K100LV CR polymers were used as rate retarding agents in nine formulations (F-1 to F-9). The granules were evaluated for angle of repose, loose bulk density, tapped bulk density, Carr’s index, Hausner ratio, moisture content, total porosity and assay. The tablets were subjected to diameter, thickness, assay, uniformity of content, assay after 1Month at 40°C+75%RH, hardness, friability, and in vitro dissolution studies. The granules showed satisfactory flow properties, compressibility, and drug content. All the tablet formulations showed acceptable pharmacotechnical properties and complied with pharmacopoeial specifications for tested parameters. The in vitro dissolution study was carried out for 8 hour using USP-2009 Apparatus-I (Rotating basket method) in distilled water as the dissolution medium. The release mechanisms were explored and explained by Zero order, First order, Higuchi, Korsmeyer-Peppas and Hixson-Crowell equations. Nine formulations were prepared by using three variable ratio of two polymers; Methocel K15M CR (25%, 20% and 15%) and Methocel K100LV CR (15%, 10% and 5%) where all the formulations (F-1 to F-9) contained 0.5% colloidal silicon dioxide and 1% magnesium stearate. Among these nine formulations, six formulations; F-2 (Methocel K15M CR: Methocel K100LV CR = 25% : 10%), F-3 (Methocel K15M CR : Methocel K100LV CR = 25% : 5%), F-4 (Methocel K15M CR : Methocel K100LV CR = 20% : 15%) F-5 (Methocel K15M CR: Methocel K100LV CR = 20% : 10%), F-6 (Methocel K15M CR : Methocel K100LV CR = 20% : 5%) and F-7 (Methocel K15M CR : Methocel K100LV CR = 15% : 15%) met the official specification of release profile. It was also found that the type and the amount of polymers significantly affect the time required for 50% (T50% or MDT) of drug release, release rate constant and diffusion exponent. Higher the MDT value indicates a higher drug retaining capacity of the polymers and vice-versa. Kinetic modeling of in vitro dissolution profiles revealed the drug release mechanism of all proposed formulations followed anomalous type or non-Fickian transport (n>0.43 and n<0.85). These studies explored both of the optimum concentration and effect of polymers on Nitroglycerin release pattern from the tablet matrix for 8 hour period.
Table of Contents
- CHAPTER 1: INTRODUCTION
- 1.1 Introduction
- 1.2 Historical viewpoints of controlled release drug delivery
- 1.3 Sustained release drug delivery system
- 1.3.1 Concept of sustained release drug delivery system
- 1.3.2 Rationale of sustained release drug delivery system
- 1.3.3 Oral sustained release drug delivery system
- 1.3.4 Advantages of sustained release dosage forms
- 1.3.5 Disadvantages of sustained release dosage forms
- 1.3.6 Drugs unsuitable for sustained release dosage forms
- 1.3.7 Factors affecting sustained release dosage forms
- 1.3.7.1 Physicochemical properties of the drug affecting sustained release dosage forms
- 1.3.7.2 Biological properties of the drug affecting sustained release dosage forms
- 1.3.8 Formulation methods used to prepare sustained release dosage forms
- 1.3.8.1 Particle size modification
- 1.3.8.2 Matrix system
- 1.3.8.3 Coating system
- 1.3.8.4 Beads and sphere
- 1.3.8.5 Enteric coated beads in capsule
- 1.3.8.6 Mixed release granules
- 1.3.8.7 Repeated action tablets
- 1.3.8.8 Erosion core with initial dose
- 1.3.8.9 Erosion core only
- 1.3.8.10 Ion exchange resin
- 1.3.8.11 Complexation
- 1.3.8.12 Microencapsulation
- 1.3.8.13 The osmotic tablet
- 1.3.8.14 Gel forming hydrocolloids
- 1.3.8.15 Environmentally responsive system
- 1.3.9 Methods and mechanisms of sustaining drug action
- 1.3.9.1 Diffusional systems
- 1.3.9.2 Dissolution controlled system
- 1.3.9.3 Water penetration controlled system
- 1.3.9.4 Chemically controlled systems
- 1.3.9.5 Hydrogels
- 1.3.9.6 Ion exchange resins
- 1.3.10 Technical sophistication based classification of sustained release drug delivery
- 1.4 Matrix devices
- 1.4.1 Polymers used in matrix devices
- 1.4.2 Properties of an ideal polymer
- 1.4.3 Classification of polymers
- 1.4.3.1 Matrix devices with insoluble inert polymer
- 1.4.3.2 Matrix devices with insoluble erodible polymer
- 1.4.3.3 Matrix devices with hydrophilic polymer
- 1.4.3.4 Matrix devices with hydrogel polymer
- 1.4.4 Use of excipients in matrix devices
- 1.4.5 Release mechanisms from matrices
- 1.4.6 Mathematical models of release mechanics from matrices
- 1.4.6.1 Release from soluble retardants
- 1.4.6.2 Release from insoluble retardants
- 1.4.6.3 Drug release of low solubility in eluting media
- 1.4.6.4 Exponential model
- 1.4.6.5 Geometric dependence of diffusion exponent (n) and variation of n values with mechanism of diffusion
- 1.5 Thesis topic
- 1.5.1 Rationale
- 1.5.2 Active component
- Sustained-release drug delivery systems and their advantages/disadvantages.
- Formulation methods for sustained-release dosage forms, including matrix systems and other techniques.
- Factors affecting sustained release, such as physicochemical and biological properties of the drug.
- Mathematical models describing drug release mechanisms from matrices.
- The specific application of these principles to the design and evaluation of nitroglycerin sustained-release tablets.
Objectives and Key Themes
This dissertation aims to explore the formulation design and evaluation of nitroglycerin sustained-release tablets. It investigates various aspects of sustained-release drug delivery systems, focusing on the specific challenges and opportunities presented by nitroglycerin.
Chapter Summaries
CHAPTER 1: INTRODUCTION: This introductory chapter provides a comprehensive overview of sustained-release drug delivery systems. It delves into the historical context, exploring the evolution and rationale behind this approach to drug administration. The chapter meticulously examines the advantages and disadvantages of sustained-release formulations, along with factors influencing their effectiveness, including the physicochemical and biological properties of the drug itself. Furthermore, it details various formulation methods used to achieve sustained release, ranging from particle size modification and matrix systems to coating techniques and more advanced approaches like osmotic tablets and environmentally responsive systems. A significant portion of the chapter is dedicated to the different mechanisms by which sustained drug action is achieved, encompassing diffusional systems, dissolution-controlled systems, and chemically controlled systems. Finally, the chapter introduces the thesis topic—the formulation and evaluation of nitroglycerin sustained-release tablets—and provides a rationale for this specific focus, highlighting the significance of sustained-release delivery for nitroglycerin and the research gaps the study intends to address. The chapter lays the groundwork for the subsequent chapters, establishing the theoretical foundation and providing context for the practical aspects of the research.
Keywords
Nitroglycerin, sustained release, drug delivery, tablet formulation, matrix systems, polymers, drug release mechanisms, pharmaceutical technology, bioavailability, controlled release.
Frequently Asked Questions: A Comprehensive Language Preview of Sustained-Release Nitroglycerin Tablets
What is the overall topic of this document?
This document provides a comprehensive preview of a dissertation focused on the formulation design and evaluation of nitroglycerin sustained-release tablets. It covers the theoretical background of sustained-release drug delivery systems, various formulation methods, and the application of these principles to nitroglycerin.
What are the key themes explored in the dissertation?
Key themes include: sustained-release drug delivery systems and their advantages/disadvantages; formulation methods for sustained-release dosage forms (matrix systems, coating, etc.); factors affecting sustained release (physicochemical and biological properties of the drug); mathematical models describing drug release mechanisms from matrices; and the specific application of these principles to nitroglycerin sustained-release tablets.
What is the structure of the dissertation preview?
The preview includes a table of contents, objectives and key themes, chapter summaries, and keywords. The table of contents provides a detailed breakdown of Chapter 1, which serves as an introduction to the subject matter.
What are the main topics covered in Chapter 1 (Introduction)?
Chapter 1 offers a broad overview of sustained-release drug delivery systems, including historical viewpoints, the rationale behind sustained release, advantages and disadvantages of such systems, and various formulation methods (e.g., particle size modification, matrix systems, coating systems, osmotic tablets). It also discusses the mechanisms of sustained drug action (diffusional, dissolution-controlled, chemically-controlled systems) and introduces the thesis topic: the formulation and evaluation of nitroglycerin sustained-release tablets.
What are the different formulation methods for sustained-release dosage forms discussed?
The document mentions numerous methods, including particle size modification, matrix systems, coating systems, beads and spheres, enteric coated beads in capsules, mixed release granules, repeated action tablets, erosion core systems, ion exchange resins, complexation, microencapsulation, osmotic tablets, gel-forming hydrocolloids, and environmentally responsive systems.
What types of polymers are discussed in relation to matrix devices?
The preview mentions various types of polymers used in matrix devices, categorized by their properties: insoluble inert polymers, insoluble erodible polymers, hydrophilic polymers, and hydrogel polymers. The document also discusses the properties of an ideal polymer for such applications.
What mathematical models are used to describe drug release mechanisms?
The preview mentions mathematical models for release from soluble and insoluble retardants, drug release of low solubility in eluting media, the exponential model, and a model focusing on the geometric dependence of the diffusion exponent (n) and its variation with the mechanism of diffusion.
What is the specific focus of the dissertation?
The dissertation focuses on the formulation design and evaluation of nitroglycerin sustained-release tablets. This involves investigating the challenges and opportunities associated with delivering nitroglycerin using sustained-release technology.
What are the keywords associated with this dissertation?
Keywords include: Nitroglycerin, sustained release, drug delivery, tablet formulation, matrix systems, polymers, drug release mechanisms, pharmaceutical technology, bioavailability, controlled release.
- Quote paper
- Subrata Bhadra (Author), 2010, Nitroglycerin Sustained Release Tablet. Formulation Design and Evaluation, Munich, GRIN Verlag, https://www.grin.com/document/231784
