Handbook of Polymers for Pharmaceutical Technologies, Processing and Applications

Vijay Kumar Thakur, Manju Kumari Thakur, Vijay Kumar Thakur, Manju Kumari Thakur

• Publisher: Wiley-Scrivener
• Year: 2015
• ISBN:
  9781119041399
• Edition: 1
• Topic: Technology & Engineering
• Subtopic: Chemical & Biochemical Engineering
• Index: Technology & Engineering

Polymers are one of the most fascinating materials of the present era finding their applications in almost every aspects of life. Polymers are either directly available in nature or are chemically synthesized and used depending upon the targeted applications. Advances in polymer science and the introduction of new polymers have resulted in the significant development of polymers with unique properties. Different kinds of polymers have been and will be one of the key in several applications in many of the advanced pharmaceutical research being carried out over the globe.

This 4-partset of books contains precisely referenced chapters, emphasizing different kinds of polymers with basic fundamentals and practicality for application in diverse pharmaceutical technologies. The volumes aim at explaining basics of polymers based materials from different resources and their chemistry along with practical applications which present a future direction in the pharmaceutical industry. Each volume offer deep insight into the subject being treated.

• Volume 1: Structure and Chemistry
• Volume 2: Processing and Applications
• Volume 3: Biodegradable Polymers
• Volume 4: Bioactive and Compatible Synthetic/Hybrid Polymers

Chapter 1

Particle Engineering of Polymers into Multifunctional Interactive Excipients

Sharad Mangal, Ian Larson, Felix Meiser and David AV Morton*

Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia

*Corresponding author: [email protected]

Abstract

Both natural and man-made polymers are widely utilized as tablet binders and filler-binders. The physicochemical and mechanical properties such as particle size, shape and deformation behavior of polymeric binders are key in their effective use. Many such binders are applied as solution in a wet granulation process, which facilitate its facile distribution leading to improved effectiveness as a binder. Direct compression and dry granulation are recognized as routes with reduced process complexity and cost. These processes require a binder to be employed in a dry form and it can be more difficult to obtain a homogeneous distribution of a dry binder in a powder formulation. Therefore, these binders are required in high proportions to generate mechanically strong tablets. At lower proportions, they often are insufficient to create mechanically strong tablets. Recently, innovations in the generation of co-processed excipients have been proposed. Co-processing is a popular means of improving excipient functionalities, where two or more existing excipients are combined by some suitable means to generate new structures with improved and often combined functionalities as compared to the component excipients. Particle size reduction is known to improve the binder properties of an excipient, but also makes it highly cohesive and hard to blend. Via particle engineering, surface structure of smaller particles can be tailored to optimize the cohesive-adhesive balance (CAB) of the powder, allowing formation of interactive mixtures. This chapter reviews recent efforts to engineer surface-modified polymeric micro-excipient structures with the inherent ability to not only form an interactive mixture efficiently and provide flow enhancement, but also to create harder tablets at lower proportions. Hence, this approach represents a potential novel multifunctional prototype polymeric micro-excipient for direct compression and dry granulation processes.

Keywords: Particle engineering, powder technology, interactive mixtures, tablets, binder, multifunctional excipients

1.1 Introduction

The modern pharmaceutical market is under relentless pressure from slowing new product approvals, patent expiries and global competition. In addition, new opportunities exist with an evolving patient population, numerous unmet medical needs and growing disease awareness. The pharmaceutical industry must evolve and improve product developing and manufacturing efficiencies for sustainable performance. Efficient and cost-effective product development and manufacturing are continually being explored to meet the challenge of not only reducing cost but also reducing the risk of product recalls.

Tablets are the most commonly used pharmaceutical preparation, accounting for more than 80% of all dosage forms administered [1]. The principal reasons for their continued popularity include convenience of administration and patient preference, high-precision dosing, stability and cost effectiveness [2].

Tablets are typically manufactured by applying pressure to active pharmaceutical ingredient(s) (APIs) and excipients powder blends in a die using a punch, which compresses the powder into a coherent compact. Under compression, bonds are established between the particles, thus conferring a certain mechanical strength to the compact. A formulation must exhibit good flow and high compactability for an API to be transformed into tablets of satisfactory quality. Good flow is necessary to ascertain the rapid and reproducible filling of powder into the die to minimize weight variation; while high compactability is required to ensure that the tablets are sufficiently strong to withstand handling during manufacturing and transportation [3].

The majority of API(s) lack the requisite flow and compactability for direct tablet manufacturing [4]. Therefore, the flow and compactability of the API(s) need to be adjusted to ensure formation of high-quality tablets. Typically, the flow and compactability of a tablet formulation is improved by a granulation step (wet or dry granulation) in which the particles of API(s) and excipients are agglomerated into larger particulate structures referred to as granules. Wet granulation of the input materials can improve the flow properties for further processing and can create non-segregating blends of powder ingredients [5]. However, it involves multiple manufacturing steps, which can add significant time and cost to the process. Conversely, direct compression merely involves mixing of API(s) and excipients followed by immediate compression (Figure 1.1). Therefore, direct compression is an attractive manufacturing process, with fewer steps, for reducing cost and improving manufacturing output.

Figure 1.1 The various steps involved in wet granulation, dry granulation and direct compression tablet manufacturing.

Adapted and modified from [6].

1.2 Polymers as Excipients

Excipients form an integral part of any pharmaceutical tablet formulation. They play the fundamental role in creation of robust tablet formulations by carrying out an extensive range of functions such as fillers, binders, disintegrants, lubricants, glidants, coating agent and anti-adherents. Currently, a wide range of polymeric materials are used as excipients [6,7], and polymers are the largest overall consumed product segment for the global excipients market, accounting for over 30% [8]. The excipient market is expected to grow at an annual rate of 5.2% from 2013 to 2018, to reach around $7.35 billion by 2018 [8].

Polymers of natural, semi-synthetic and synthetic origin are used especially in the role of binder and filler-binder (see Table 1.1). Polymeric excipients are popular as they can be tailored for many applications by altering their chain length and by chemical functionalization. This can achieve new materials with various optimized physicochemical and mechanical properties for such specific applications.

Table 1.1 List of polymeric excipients, their source and functionalities. This table is compiled from the information given in the Handbook of Pharmaceutical Excipients [9].

Polymeric Excipient	Source	Functionality
Natural
Zein	Extracted from corn gluten	Binder, Coating agent
Cellulose	Extracted from fibrous plant material	Diluent, Disintegrant
Alginic acid	Extracted from various species of brown seaweed	Binder, Disintegrant
Acacia	Exudate from the stems and branches of Acacia Senegal	Binder
Guar gum	Extracted from the endosperm of the Cyamopsis tetragonolobus	Binder, Disintegrant
Inulin	Extracted from the tubers of Dahlia variabilis, Helianthus	Binder
Chitosan	Extracted from shells of crustaceans such as shrimps and crabs	Binder, Coating agent
Semi-synthetic
Sodium alginate	By neutralized alginic acid with sodium bicarbonate	Binder, Disintegrant
Calcium alginate	By treating sodium alginate with calcium salts	Disintegrant
Methyl cellulose	By treating wood pulp with alkali followed by methylation	Binder, Disintegrant, Coating agent
Carboxymethyl cellulose sodium	By treating wood pulp with alkali followed by reaction with sodium monochloroacetate	Binder, Disintegrant
Carboxymethyl cellulose calcium	By treating wood pulp with alkali followed by methylation and then converting to calcium salt	Disintegrant
Cellulose acetate	By treating cellulose with acid catalysis and acetic anhydride	Diluent, Coating agent
Cellulose acetate phthalate	By reacting cellulose acetate with phthalic anhydride	Coating agent
Microcrystalline cellulose	By controlled hydrolysis of cellulose with mineral acid	Binder, Diluent, Disintegrant
Hydroxypropylmethyl cellulose	By treating alkali cellulose with chloromethane and propylene oxide	Binder, Coating agent
Hydroxypropylmethyl cellulose acetate succinate	By the esterification of hydroxypropylmethyl cellulose with acetic anhydride and succinic anhydride	Film coating, Enteric coating
Hydroxypropylmethyl cellulose phthalate	By the esterification of hydroxypropylmethyl cellulose with phthalic anhydride	Enteric coating
Ethylcellulose	By ethylation of the alkali cellulose with chloroethane	Binder, Diluent, Coating agent
Low substituted-hydroxypropyl cellulose	By reacting alkaline cellulose with propylene oxide	Binder, Disintegrant
Ethyl cellulose	By ethylation of the alkali cellulose with chloroethane	Binder, Diluent, Coating a...