UNDERSTANDING THE MANUFACTURING PROCESS OF ORAL SOLID DOSAGE FORMS

Despite several novel dosage forms being introduced into the pharmaceutical and nutraceutical sectors, oral solid drugs (OSD), particularly tablets and capsules, continue to be the most popular and widely used delivery forms, owing to their various advantages, including self-administration, stability, cost-effectiveness, convenience of handling, transportation and patient compliance. This mature yet high-value vertical within the overall pharmaceutical industry represents about 90% of the global market share of all formulations intended for human use.

The growing demand for complex oral solid formulations indicated for use with different indications necessitate customized production techniques and facility designs. Moreover, rapid scale-up / scale-out of the OSD manufacturing operations is a complex process requiring specialized equipment and facilities, highly contained working environments and experts with multidisciplinary knowledge. Further, recent evolution to address the upstream bottlenecks associated with API, such as poor bioavailability, low solubility, bitter taste and high potency, necessitate extensive technical expertise. As a result, drug developers are increasingly relying on contract service providers to leverage their capabilities and yield cost savings opportunities. The global oral solid dosage market is anticipated to grow at a CAGR of around 5%, till 2035, according to Roots Analysis. Driven by the immense popularity of oral solid dosage forms, especially amongst the pediatric and geriatric populations, we believe that the demand for conventional as well as modified oral solid formulations is likely to drive commendable market growth within the oral solid dosage contract manufacturing market during the forecast period.

OVERVIEW OF ORAL SOLID DOSAGE FORMS

The oral solid dosage (OSD) form refers to a formulated product that is ingested through the mouth and absorbed through the digestive tract to different parts of the body. It is interesting to note that

 some solid medicated preparations are designed to integrate in the oral cavity and absorb through the mucous membranes of the mouth, for rapid therapeutic effect. The oral solid dosage forms are processed (blended, milled, granulated, dried, tableted, or encapsulated), along with the APIs in order to produce the required type of oral solid finished drug product. The successful preparation of an optimum tablet formulation is dependent upon the type of excipient added to the formulation.

MANUFACTURING OF ORAL SOLID DOSAGE FORMS

Manufacturing of oral solids involves a series of unit operations to convert raw materials into orally ingested finished dosage forms. The various steps involved in the manufacturing of oral solids, specifically tablets, have been briefly described below:

• Weighing / Dispensing: It includes sampling of raw materials for quality purposes. These raw materials typically include APIs, excipients, primary and secondary packaging, and cleaning agents.

• Feeding / Material Handling: It involves accurate and consistent mixing of the APIs with other raw materials while avoiding / minimizing any contamination. Primary challenges involved in this process include poor flowing nature of raw materials and feeding very low levels of APIs, specifically high potency forms.

• Blending: In order to ensure a homogenous composition, the raw materials are subjected to blending, prior to downstream process steps. Commonly used methods include tumble blending, bin blending and agitator mixers.

• Direct Compression: It involves compressing of powder blends of API with the excipient(s), without any pre-mechanical treatment. However, this method is not ideal for high-dose APIs, due to difficulty in calibrating the flow and compaction properties and very low-dose APIs.

• Granulation: Granulation is the process of combining / agglomerating particles into a granule. Granulation processes can be classified into dry granulation and wet granulation. Dry granulation is used to process APIs that are sensitive to solvents, heat and moisture. The procedure involves mechanical compression or compaction of powder mixture with a dry binder to facilitate the particle agglomeration. Wet granulation, the most commonly used method for tablet processing, involves wet massing of the API and excipients with granulation liquid (water and / or ethanol), followed by sizing and drying of wet granules.

• Milling / Sieving: This process involves breaking oversized granules and homogenizing the granule size by screening. The cut-off screen size depends on the desired pharmacological performance of the drug.

• Coating: This process involves the application of coating material on the surface of the tablet to achieve desirable properties. These properties include improving taste, odor and color of the drug, enabling ease of swallowing, improving product stability, protecting the API against the gastric environment, improving the mechanical resistance of dosage form and modifying release properties.

ADVANTAGES OF ORAL SOLID DOSAGE FORM:

• High Patient Compliance
• Availability in variety of custom shapes, size and colors as per demand
• Cost effective
• Safe route of administration
• Availability of taste and odor masked formulations
• Less sterility concerns
• Convenient for repeated and prolonged use

DISADVANTAGES OF ORAL SOLID DOSAGE FORM:

• Swelling problem in pediatric and geriatric populations
• Relatively slow onset of action
• Complexity of coating encapsulation process
• Bioavailability issue
• Not suitable for administration of drugs that are destroyed by gastric acid
• Requirement of patient’s compliance for optimum therapeutic effect

EMERGING TRENDS IN ORAL SOLID DOSAGE MANUFACTURING

Owing to evolving customer demands and continual updates to regulations, innovator companies and manufacturers of OSD products must incorporate technological and process improvements in order to maintain dominance in the overall pharmaceutical sector.³⁶ In the recent years, various platforms have been introduced to facilitate OSD delivery, bioavailability, quality, efficacy, safety, presentation and marketing, to improve the affiliated manufacturing processes. Some of the emerging trends in the OSD manufacturing domain have been summarized below:

• Digital Pills: This technology combines traditional pills with a monitoring system, an ingestible sensor, that automatically records data about medication adherence as well as patients’ physiological data. It is interesting to note that the first digital pill, Abilify Mycite, was approved by the FDA in 2017.

• 3D Printing: 3D printing (3DP), also known as additive manufacturing, is a method of manufacturing involving the layer-by-layer deposition of materials to create a final product according to a digital model. The compression forces in the traditional tableting machines produce heat, thereby, impacting a pill’s molecular structure, dissolution rate, bioavailability, and overall efficacy.

• Process Analytical Technology (PAT): Process analytical technology (PAT), introduced by FDA in 2004, is a system for designing, analyzing and controlling pharmaceutical manufacturing processes through measurements of critical quality and performance attributes of raw and processed materials to ensure final product quality.

• Digital Twin: A digital twin is a virtual representation of an object that is updated from real- time data, and uses simulation, machine-learning and reasoning to help decision making. In October 2019, a partnership was inked to develop a digital twin of the continuous direct compression (CDC) platform in order to optimize the formulation process of oral solid dosage forms in digital space, and thereby, reduce the raw material and time required during the initial processes.

FUTURE PERSPECTIVES

The oral solid dosage market is the largest segment in the pharmaceutical industry, which is anticipated to reach over USD 900 billion by 2027. Considering the popularity of oral dose pharmaceutical products, it is highly improbable to be replaced with an alternative drug delivery technique, in the near future. In this competitive and growing market, outsourcing has evolved into a viable and profitable business model. Although it is mostly the small and mid-sized players that opt to recruit the services of contract service providers, some of the larger and more established players are also known to outsource certain aspects of oral solid dosage development and manufacturing. In fact, the shift away from blockbuster drugs toward targeted therapies based on more complex APIs produced in smaller volumes has created challenges for pharmaceutical companies manufacturing large volume commodity products. As a result, they partner with CDMOs and CMOs having specialized drug delivery technologies that are not cost-effective for drug developers to invest in but offer competitive advantages. Unlike drug developers, the capabilities of these third-party service providers are usually more focused on their respective service portfolios. They support pharmaceutical companies with specialized capabilities ranging from process and formulation development to drug substance characterization, analytical method development, and regulatory filings, as well as capacity for clinical and commercial manufacturing. Moreover, such companies ensure that they have the latest upgrades in equipment and infrastructure, in order to improve the quality of services offered. In fact, in the recent past, a number of contract manufacturers have forged strategic alliances with and / or acquired other players, in order to further enhance their portfolio of offerings for oral solid dosage forms. Considering the growing trend of outsourcing and the ongoing efforts of service providers to improve / expand their offerings, we believe that the oral solid dosage contract manufacturing market is likely to evolve at a steady pace, in the mid to long term.

Roots Analysis is a global leader in the pharma / biotech market research. Having worked with over 750 clients worldwide, including Fortune 500 companies, start-ups, academia, venture capitalists and strategic investors for more than a decade, we offer a highly analytical / data-driven perspective to a network of over 450,000 senior industry stakeholders looking for credible market insights. All reports provided by us are structured in a way that enables the reader to develop a thorough perspective on the given subject. Apart from writing reports on identified areas, we provide bespoke research / consulting services dedicated to serve our clients in the best possible way.