Oral Controlled Drug Delivery by Hot-Melt Extrusion Technology

Introduction

Each delivery technique has advantages and disadvantages, and each necessitates the construction of a specialized delivery vehicle. Oral delivery has emerged as the most appealing approach among the numerous options, owing to its ability to produce solid formulations with a long shelf life, sustained release, the convenience of administration, and enhanced biological response (Araújo et al., 2017; Choi et al., 2013). Furthermore, a vast surface area (>300 m²) lined with a viscous mucosal layer facilitates active component adhesion and absorption (Ensign et al., 2012; Schenk and Mueller, 2008). The absorption mechanism of oral medications, however, is more complex than that of other routes. To be absorbed in the stomach, small intestine, or colon, oral medication must be soluble in gastric fluid. The conventional oral pharmaceutical preparations also have a rapid drug release and a major fluctuation in plasmatic drug concentration, necessitating repeated administrations (chiefly for drugs with a short half-life). To overcome these limitations and achieve a greater therapeutic effect, new pharmaceutical systems are highly encouraged (Jlassi et al., 2017). The goal of controlled drug delivery systems (CDDS) is to precisely administer small amounts of active agents in small volumes to specific regions in the body, hence improving drug use. This aids in keeping drug concentrations in the blood or target tissues as consistent as possible for a long period. To achieve a successful therapeutic concentration of the drug rapidly, CDDS usually releases a portion of the dose initially. Further, a well-defined release kinetics pattern is observed to achieve the maintenance dose allowing the attainment of the target drug concentration (Dash et al., 2010). Releasing the drug in a controlled fashion over a longer period is highly advantageous for drugs that are quickly metabolized and eliminated from the body after administration. In the traditional system, only the total amount of drug delivered to a patient is controlled. However, in CDDS, both the amount of the active and the rate at which it is administered are regulated. This helps in monitoring and improving several drugs' safety and effectiveness (Meyers, 2002).

In the field of pharmaceutical science, novel technologies are being exploited to develop oral CDDS in light of their versatile applications. Melt extrusion has evolved from a novel formulation technique to an important platform technology in the drug development process over the years. The overwhelming amount of lipophilic active pharmaceutical ingredients (APIs) entering the development cycle has caused this paradigm change. Extrusion is the technique of driving a raw material through a die under regulated conditions to produce a product with a uniform shape and density. Extrusion can be performed in a continuous mode, allowing for a steady product flow at relatively high throughput rates. Owing to the potential advantages of the HME technique in developing a plethora of dosage forms for varied applications and the fact that it supports process analytical technology (PAT) along with quality by design approach (QbD), HME has gained remarkable attention in the pharmaceutical industries. This chapter has a three-fold aspiration. First, to introduce CDDS, their historical perspective, fundamental drug release mechanisms, challenges that lie ahead for the pharmaceutical industry, and current advancements made in CDDS. The second part of the chapter emphasizes the basic concepts, process, and equipment design of HME. The third part highlights the applications of HME in the development of various CDDS such as sustained-release oral drug delivery, gastroretentive, chronotherapeutic drug delivery system, bioadhesive films, colon-specific, etc. HME can function alone or in combination with other down streaming ancillary equipment such as a high-pressure homogenizer, miller, pelletizer, roller, and a 3D printer to develop above mentioned controlled release (CR) formulations. Overall, this chapter presents an overview of the significance of HME in the development of oral CDDS to motivate researchers for implementing HME as continuous manufacturing (CM) tool in the pharmaceutical industry.