Advancements In Excipient Characterization For The Optimization of Oral Solid Dosage Forms: From Characterization To Formulation.

Oral solid dosage (OSD) forms are the most widely used forms to deliver pharmaceuticals. In the 2010-2019 decade, the oral administration represented the dominant route among the New Molecular Entities (NMEs) approved by Food and Drug Administration (FDA) [1]. According to the recently published report of FDA’s new drug approvals in 2023, 55 drugs were authorized for the market and, among these, 24 drugs required an oral administration (44%); the remaining part was represented by other administration routes (intravenous, pulmonary, ocular and topical) [2]. In particular, Tablets represented the 27% of all new drugs approved, followed by capsules (13%) with a total percentage of OSD of almost 40% only in 2023’s new drugs approved. Therefore, this report confirms the primary role that oral solid dosage (OSD) forms still play in the pharmaceutical industry. Despite minor fluctuations over the last few years, OSD remains the primary formulation choice. OSD forms have several advantages in terms of cost-effectiveness, convenience of manufacturing, well-established production processes, ease of administration and high compliance among patients. Their chemical and physical stability is enhanced by the solid-state form and also storage and transport are simpler than that of other dosage forms. In essence, the advantages of OSDs provide a strong impetus to their market, encouraging continued and increased usage. Estimates suggest that the profits generated with OSDs will reach 1.03 trillion USD in 2032, compared to the current 524.6 billion. [3]. OSDs include tablets, capsule, powders, granules and most of these are also easily handled to obtain controlled release pharmaceutical forms (i.e., enteric coated capsules and tablets). Besides these, new formulations approved by FDA could offer significant advances in the OSD field, such as chewable tablets and capsules [2] or fast dissolving tablets [4], both suitable for paediatric, dysphagic and bed-ridden patients. OSDs are commonly well accepted by patients, but there are some categories of them to which a solid oral therapy cannot be prescribed and administered, specifically the paediatric population, patients who are in a state of unconsciousness and dysphagic patients. Regarding the first, despite an increasing interest about the paediatric drugs and appropriate formulations, there is still a lack of age-appropriate medications in the market [5]. To solve this problem, manipulation of the medicines has become a common practice, together with the tailored formulation of paediatric drugs in galenic laboratories. New formulations approved to overcome this problem have been developed, such as oral- soluble tablets, oral films and sublingual dosage forms [5], but there is still room for improvement to guarantee an appropriate therapy for these patients. These improvements would as well be suitable for dysphagic patients, a group of population affected by difficulties or inability in swallowing. This is not a marginal issue because it is estimated that the incidence of dysphagia in patients over 65 years old ranges from 7% to 13% [6] and this number is expected to increase with the awaited increase of the average lifespan. Caregivers of dysphagic patients are often in need of a proper formulation that could be administered to them and, as a result of the lack of appropriate dosage forms, they manipulate the drugs in order to obtain a suitable dosage form. These manipulations include the solubilization of tablets, opening of capsules and tablet splitting. However, this process is not only risky because it is an “off-label” use of the medicine, but the splitting of medicines that were originally in the form of capsules or tablets has been correlated to the appearance of adverse effects [7]. Hopefully, in the next future more efforts will be taken to guarantee age-appropriate formulations available in the market. The formulation of an OSD form presents several challenges to the formulation scientists, first of all the choice of the excipients. The excipients in a formulation could have different roles, for instance they could be necessary to carry out the production without process disruptions or they could just have an aesthetic role. While the former role may seem the most important aspect of the manufacturing process, the aesthetic role also plays a fundamental role in patients’ compliance. In fact, several studies demonstrated that different colours help in the identification of the products, especially for patients in polytherapy, and it was also demonstrated how the colour has a psychological impact [8]. Amawi and Murdoch [9] proved that the colour of the pills has a notable impact on the efficacy perceived by patients and they also showed how different colours are more impactful for a disease than another. For instance, the blue and white was the most chosen among patients in need for a sedative medicine, red pills were the most chosen among stimulants and both yellow and red were the most chosen for the hallucinogenic category. Table 1 displays some of the widely used classes of excipients for OSDs, together with a few examples for each class and their role in the formulation [10] [11].In this chapter, OSD forms will be discussed both from a technological and formulative point of view, to explain the process robustness and the challenges that the formulator has to face in the daily practice. First, a general introduction to the manufacturing methods of tablets will be provided, followed by an overview of the properties of bulk solids that directly influence the formulation and selection of manufacturing methods. Moreover, a general introduction on the OSDs (mainly tablets and capsules) coating will be reported.