The pharmaceutical excipients are substances, other than drug substance, which have been appropriately evaluated for safety and are included in drug delivery system to aid the processing of the delivery system during its manufacture; protect, support or enhance stability, bioavailability or patient acceptability; assist in product identification or enhance any other attribute of the overall safety and effectiveness of drug during storage and use.
The pharmaceutical excipient industry is driven by multifaceted demands. Worldwide, pharma excipient experts identify several trends driving excipient demand, solubility and bioavailability challenges, the reduced research and development productivity, downward price pressure, stringent regulation, desire to increase the lifecycle of a drug, improve manufacturing efficiency and address the growing bioequivalence market have forced drug makers to increasingly turn to excipients with the intent to develop drug products at low cost without compromising quality. Global forecast reports by Marketsandmarkets Research Private Ltd., suggest that the market trend for solubility enhancement excipients grow at a compound annual growth rate of nearly 13 per cent in the period from 2014 to 2024; and the overall pharmaceutical excipients market is expected to be valued at $8.43 billion by 2019, up from $5.76 billion in 2013.
Selection of pharmaceutical excipients for a drug formulation is an important step in formulations’ development. Proper screening and selection of excipient may reduce manufacturing costs by being multifunctional in terms of enhancing the solubility of drug, improving its bioavailability and enhanced physiochemical stability. The right excipient will have the ideal pharmacokinetic profile for intended pharmaceutical application and work well with existing equipment or fit into manufacturing plan. Several experts from pharmaceutical excipient industry, aver significance and role of various excipients in formulating and manufacturing drug products for improved bioavailability, solubility, and drug delivery.
Lipid based drug delivery systems are effective for hydrophobic drugs when designed with careful selection of excipients. Lipids are not only varying in structures and physio-chemical properties, but also in their digestibility and absorption pathway. Consequently, the selection of lipid excipients has a pronounced effect on the biopharmaceutical aspects of drug absorption and distribution. A wide range of novel lipid excipient with acceptable regulatory and safety profiles is available for screening as carriers for delivering hydrophobic drugs with low bioavailability, and for optimal solubilization of the drug.
Gattefossé excipients like Labrasol®, Labrafil® M1944, and Gelucire® 44/14, which form fine dispersions once in contact with aqueous phase, lead to enhancement of bioavailability. Main feature of excipients like Labrasol and Gelucire 44/14 is their ability to solubilize the drug in the GIT and improve its permeability. Surfactant based excipients can facilitate the solubilization of lipophilic drugs by micelle formation or by acting as co-solvents. Polyglycol glycerides are useful in preparing lipid-based formulations that can significantly enhance solubility and therefore oral bioavailability using various self-emulsifying systems. Abitec develops lipid-based excipients (CAPTEX®, CAPMUL®, and ACCONON®) to enhance bioavailability of poorly water soluble and poorly permeable drug for the pharmaceutical industry. Moreover, Fuji’s specialty excipients, Neusilin® and Fujicalin®, having high specific surface area with a mesoporous structure, provides a high oil adsorption capacity and can convert the lipid-based delivery system into a freely flowing and compressible powder that helps in enhancing bioavailability of drug.
Polymeric excipients stabilize the amorphous drug in a solid state and then maintain its supersaturation in aqueous phase. Polymeric excipients can also be used to control the release when the drug is solubilized. Ashland has experience with solid dispersion polymers, such as copovidone and hypromellose acetate succinate, as part of a broad range of cellulose and vinyl pyrrolidone polymers with excellent extrudability as well as a controlled-release property.
Since last many years, Evonik has been manufacturing EUDRAGIT poly(meth)acrylate polymers (anionic, cationic and neutral) for controlled release coatings or in matrix applications in number of pharmaceutical formulations. BASF’s Soluplus® enhances the solubility of drugs and so increases their bioavailability. The product is ideal for innovative pharmaceutical process technologies such as hot melt extrusion and spray drying. BASF has made great advances in solubilization and bioavailability enhancement during recent years through developing innovative solutions for even the toughest solubilization problems. BASF has great expertise in pharma excipient and has been a leader in developing hot melt extrusion technology solutions.
NISSO’s hydroxypropyl cellulose is a highly efficient excipient, traditionally used as a tablet binder in pharmaceutical and nutraceutical products, but with growing application in spray drying, hot-melt extrusion, and film formation. Gattefossé excipients, Gelucire® 50/13 and 48/16, due to their solid-state characteristics, are suitable for preparation of solid dispersions by hot melt extrusion or spray drying for preparation of self-emulsifying solid dosage forms.
Dow Food, Pharma and Medical has introduced a line of excipients to enable formulations of poorly soluble drugs to meet their end targets through not only final dosage form performance but also improved use in manufacturing technologies. The AFFINISOL™ polymers are cellulosic derivatives designed specifically for hot melt extrusion and spray drying applications.
Pfanstiehl’s carbohydrate based, parenteral-grade excipients such as trehalose, sucrose, mannitol, sorbitol, and maltose enable formulation scientists to stabilize large and small molecule injectable therapeutics that would otherwise not make it to the clinic due to low solubility and/or bioavailability.
Tablets are all time favourite solid oral dosage form for many reasons, including ease of manufacturing, convenience for the patient, accurate dose administration, and good stability. Colorcon’s Starch 1500 used as excipient in manufacturing of tablet is particularly effective with moisture sensitive actives and low dose applications. In addition to providing a unique range of functions and flexible performance in a variety of applications, Starch 1500 cuts process and material costs by reducing or eliminating polymeric binders, super-disintegrants, high levels of lubricants and glidants and manufacturing steps.
The global pharmaceutical excipient market will continue to grow in the near future and the growth pattern will vary among different categories of excipients. There are currently more than thousand excipients on the market and they fulfil the needs of the majority of finished pharmaceutical products. However, there is an increased recognition of the role of excipients in the drug delivery process coupled with an increased research on way to modify manufacturing process and enhance product quality by using multifunctional excipient. They play a key role in accelerating as well as enabling development of, otherwise not possible, innovative drug delivery technologies and products. Rather, they represent a category of excipients with significantly reduced development cost and regulatory hurdles when compared to creating completely new excipients with new development possibilities within the pharma industry. Following this trend, more innovative, multifunctional excipients, or specialty blends can be expected to arrive at the market in the upcoming years, having ability to reduce development costs of new product with right therapeutic index. Thus, the desire for therapeutically effective low-cost medications seems to be fulfilled, in a way, by improving the production efficacy, possible with right selection of excipients.
(Authors are faculty Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology (CHARUSAT) , Gujarat)