Co-processed excipients: an overview of formulation aspects, physical characteristics and role as a pharmaceutical-aid

About Authors: Biswajit Panda^1*, Abhinav Raoot¹, Vaishali Kilor¹, Nidhi Sapkal²
Dept of Pharmaceutics¹ and Dept of Pharmaceutical Chemistry²
Gurunanak College of Pharmacy, Nagpur

Reference ID: PHARMATUTOR-ART-1049

Abstract
Excipients are all substances contained in a dosage form other than the active substance. Tablets are the most commonly used dosage form because of the ease of manufacturing, convenience in administration, accurate dosing and stability compared to oral liquids and direct compression is the preferred method for the preparation of tablets because of several advantages. In order to justify the high rise in new drug development and high industrial output demand, new excipients with purpose satisfying characteristics are the need of the hour.New combinations of existing excipients are an interesting option for improving excipient functionality now-a-days. The current review article is prepared to have a look over the recent development in excipient technology and the approaches involved in development of such excipients. It signifies the synergistic outcome of the combination of excipients taking their material property into consideration. It also emphasises on the particular material properties in terms of physic-mechanical that are useful to overcome the limitation of existing excipients. All the developed co-processed excipients are enlisted highlighting their multi-functional and beneficial characteristics. Regulatory issues concerned with the development of new excipient are also discussed.

Introduction
Excipients are all substances contained in a dosage form other than the active substance. Solvents used for the production of a dosage form but not contained in the final product are considered to be excipients. Another definition of excipients is ‘‘Substances, other than the active drug substance or finished dosage form, which have been appropriately evaluated for safety and are included in a drug delivery system to either aid the processing of the drug delivery system during its manufacture, protect, support, enhance stability, bioavailability, or patient acceptability, assist in product identification, or enhance any other attributes of the overall safety and effectiveness of the drug delivery system during storage or use’’ (The International Pharmaceutical Excipients Council, 1995)¹. Many pharmaceutical scientists have focused their attention on the production of multifunctional excipients with enhanced performance to meet the needs of formulation experts in terms of costs of production, enhanced excipient functionality and quality of tablets.

Tablets and capsules are the most preferred dosage forms of pharmaceutical scientists and clinicians because they can be accurately dosed and provide good patient compliance, they are easy for companies to manufacture, and they can be produced at a relatively low cost. Tablets are manufactured primarily by either granulation compression or direct compression. The latter involves the compression of a dry blend of powders that comprises drugs and various excipients. The simplicity and cost effectiveness of the direct-compression process have positioned direct compression as an attractive alternative to traditional granulation technologies².Despite many research studies being conducted in the field of drug delivery, none of them have been able to match the characteristic features and advantages offered by oral unit dosage forms such as tablets and capsules. With the advent of this form of drug delivery, the subsequent researches of betterment of this delivery system emerged, which included sophisticated machinery and superior tabletting aids.

Although simple in terms of unit processes involved, the direct-compression process is highly influenced by powder characteristics such as flow ability, compressibility, and dilution potential. Tablets consist of active drugs and excipients, and not one drug substance or excipient possesses all the desired physico-mechanical properties required for the development of a robust direct-compression manufacturing process, which can be scaled up from laboratory to production scale smoothly. Most formulations (70–80%) contain excipients at a higher concentration than the active drug. Consequently, the excipients contribute significantly to a formulation’s functionality and processability. In simple terms, the direct-compression process is directly influenced by the properties of the excipients. The physico-mechanical properties of excipients that ensure a robust and successful process are good flowability, good compressibility, low or no moisture sensitivity, low lubricant sensitivity, and good machineability even in high-speed tableting machinery with reduced dwell times³. The majority of the excipients that are currently available fail to live up to these functionality requirements, thus creating the opportunity for the development of new high-functionality excipients.

Search for new excpients:
The continued popularity of solid dosage forms, a narrow pipeline of new chemical excipients, and an increasing preference for the direct-compression process creates a significant opportunity for the development of high-functionality excipients. The advantage of the existing excipient for a particular method found to be misappropriating for the other. The development of new excipients to date has been market driven (i.e., excipients are developed in response to market demand) rather than marketing-driven (i.e., excipients are developed first and market demand is created through marketing strategies) and for the past many years, very few single new chemical excipient has been introduced into the market. The primary reason for this lack of new chemical excipients is the relatively high cost involved in excipient discovery and development. However, with the increasing number of new drug moieties with varying physicochemical and stability properties, there is growing pressure to search for new excipients to achieve the desired set of functionalities and to obtain compounds having superior properties (hygroscopicity, flow ability, and compact ability) compared to the individual excipients or their physical mixtures. Hence, at this juncture development of new excipient by the modification of pre-established ones seems to be useful and justified one3.
Other factors driving the search for new excipients are;
*    The growing popularity of the direct-compression process and a demand for an ideal filler–binder   that can substitute two or more excipients
*    Tableting machinery’s increasing speed capabilities, which require excipients to maintain good compressibility and low weight variation even at short dwell times
*    Shortcomings of existing excipients such as loss of compaction of microcrystalline cellulose (MCC) upon wet granulation, high moisture sensitivity, and poor die filling as a result of agglomeration4.
*    The lack of excipients that address the needs of a specific patients such as those with diabetes, hypertension, and lactose and sorbitol sensitivity
*    The ability to modulate the solubility, permeability, or stability of drug molecules
*    The growing performance expectations of excipients to address issues such as disintegration, dissolution, and bioavailability.