Oral Solid Dosage Forms: How to Ensure Compliance and Efficacy

Introduction

Oral solid dosage forms (OSDs) comprise 66% to 70% of all prescribed and dispensed products worldwide. They include tablets, capsules, powders, and lozenges, each of which is designed to deliver active pharmaceutical ingredients (APIs) in a stable, convenient, and patient-friendly manner.

The market for oral solid dosage forms is also undergoing exponential growth. Valued at USD 645.42 billion in 2023, the OSD manufacturing market is projected to expand to USD 1,128.02 billion by 2032, growing at a CAGR of 6.4% over the forecast period (2025–2032).

However, when it comes to specific dosage forms, tablets remain the most widely prescribed and dispensed oral solid dose (OSD), capturing approximately 53.1% of the global OSD market in 2021, followed by capsules, powders, and lozenges. The widespread popularity of tablets stems from their manufacturing and logistical advantages and their preference over other dosage forms among patients and healthcare providers.

Despite their immense use, ensuring compliance and efficacy of oral solid dosage forms remains integral and requires an understanding of regulatory expectations and scientific principles. Regulatory authorities like the FDA, EMA, and WHO have established stringent guidelines to regulate the design, testing, and manufacture of OSDs, complying with which is essential for market approval and to safeguard product quality, stability, and patient safety.

At the same time, achieving therapeutic efficacy of these drugs requires precise control over formulation variables, bioavailability, and release kinetics so that the drug performs as intended in real-world clinical settings.

In this article, we will cover all factors pertaining to ensuring compliance and efficacy of oral solid dosage forms. We will also outline strategies that can be applied throughout the development lifecycle—from formulation and process design to manufacturing, quality control, and patient-centered optimization to ensure regulatory compliance and optimal therapeutic performance of oral solid dosage forms

So, without further delay, let’s dive right into the article.

What are Oral Solid Dosage Forms?

Oral Solid Dosage Forms (OSDs) are pharmaceutical drug products intended for administration via the oral route, in a solid state. OSDs are formulated into a variety of dosage forms, including tablets, capsules, caplets, etc.

Based on the required release pattern of APIs from these drug products, OSDs can be formulated as immediate release forms and modified release forms (extended release, delayed release, controlled release, and sustained release).

Tablets make up most of the OSDs, accounting for up to 53.1% market share of the oral solid dosage formulation market in 2021. The other solid forms that make up the remainder are capsules, caplets, lozenges, and powders.

According to the World Health Organization (WHO) and US FDA, OSDs are the most preferred dosage forms due to their ability to deliver consistent and controlled quantities of active ingredients with a high degree of precision.

Why OSDs Dominate the Market

OSDs remain the preferred formulation type for both manufacturers and patients because of several advantages. These include:

Convenience

OSDs are non-invasive, portable, and easy to self-administer. In fact, several studies have shown that patients prefer tablets and capsules over injections or other delivery routes due to ease of use and minimal discomfort.

Stability

Oral solid forms offer superior physicochemical and microbiological stability compared to liquids or injectables. According to the European Medicines Agency (EMA), solid dosage forms are less susceptible to degradation by heat, light, and moisture, resulting in their extended shelf life and reduced need for cold chain logistics.

Cost-effectiveness

The manufacturing, packaging, and transportation costs of OSDs are significantly lower than those of parenteral or liquid formulations.

Dosing Accuracy

OSDs allow precise quantification of the drug dose, minimizing the risk of under- or overdosing, which is critical for narrow therapeutic index (NTI) drugs.

Factors Affecting Efficacy and Compliance

Ensuring efficacy and compliance of OSDs requires a multidimensional approach that includes formulation science, manufacturing controls, and patient-centric design. Let’s briefly review each:

Formulation Design

Formulation design consists of factors like API selection, compatibility of excipients, BCS classification, solubility challenges, role of excipients, and modified-release technologies.

API Selection and Excipients Compatibility

According to the Journal of Controlled Release, physicochemical interactions between the API and excipients can impact disintegration, dissolution, and bioavailability. Therefore, the therapeutic performance of an OSD begins with the selection of the active pharmaceutical ingredient (API) and its compatibility with excipients. Incompatible combinations can lead to stability issues, reduced potency, or altered pharmacokinetics.

BCS Classification and Solubility Challenges

The Biopharmaceutics Classification System (BCS) predicts drug absorption by classifying APIs based on their aqueous solubility and intestinal permeability. BCS Class II (low solubility, high permeability) and Class IV (low solubility, low permeability) drugs pose significant formulation challenges. However, their solubility issues can be resolved by micronization, salt formation, and solid dispersion technologies.

Functional Role of Excipients

Excipients are not just inert fillers. Each excipient used to formulate an OSD serves a critical role. For example, binder support tablet integrity, disintegrants promote tablet disintegration in GIT, and coating mask bitter taste of the drug. Therefore, each component must be functionally optimized and validated through rigorous formulation testing.

Modified-Release Technologies

Advanced release mechanisms such as sustained-release, delayed-release, or pulsatile delivery systems are used to tailor the drug release profile. These systems enhance therapeutic outcomes by maintaining plasma drug levels within the therapeutic window, reducing dose frequency, and improving adherence.

Manufacturing Controls

Process Analytical Technology (PAT)

The FDA’s PAT framework encourages real-time, in-line monitoring of critical quality attributes during manufacturing. It employs techniques such as near-infrared (NIR) spectroscopy and Raman imaging to perform continuous assessment of blend uniformity, tablet hardness, and moisture content, all of which reduce batch failures and ensure consistency.

Quality by Design (QbD) Principles

QbD requires a deep understanding of the product and process design space. It requires identification of Critical Quality Attributes (CQAs) and Critical Process Parameters (CPPs) through design of experiments (DoE) and risk assessments. As a result, the quality by design methodology enhances manufacturing robustness and facilitates regulatory flexibility.

Enhancing Patient Compliance

Beyond scientific rigor, the usability of dosage from plays a central role in patient adherence in OSD (also known as patient compliance), especially in vulnerable populations such as children and the elderly.

Palatability and Swallowability

Unpleasant taste is a leading cause of non-compliance, particularly in pediatric populations. Taste-masking film coatings, made from polymers like hydroxypropyl methylcellulose (HPMC) or ethylcellulose, can resolve this issue by improving palatability of OSDs.

Pediatric Innovations: Mini-tablets and Dispersible Tablets

The WHO Pediatric Formulation Initiative recommends mini-tablets (2–3 mm) as a flexible, age-appropriate alternative to liquid formulations in children. These tablets can be administered directly or dispersed in food or liquids. When dispersed in food or liquid, these tablets offer similar advantages by disintegrating rapidly in water without losing efficacy, making them ideal for low-resource settings and pediatric use.

Dosing Convenience

Once-Daily vs. Multiple-Daily Regimens

Therapeutic regimens requiring fewer doses per day consistently achieve better adherence and patient compliance. For example, use of once-daily sustained-release formulations reduce patient burden while maintaining efficacy, especially in chronic diseases like hypertension or HIV.

Fixed-Dose Combinations (FDCs)

FDCs combine two or more APIs into a single tablet, simplifying complex regimens and enhancing compliance.

Scored Tablets for Flexible Dosing

Scored tablets allow dose titration, particularly useful for geriatrics or patients requiring gradual dose adjustment. However, scoring must be validated to ensure uniform distribution and dose accuracy, as per EMA and USP guidelines.

Patient-Centric Drug Design

Patient-centric medicines development focuses on tailoring dosage forms according to patient preferences, abilities, and diseases – all of which help improve patient compliance.

Analytical Testing and Quality Control

Ensuring efficacy and compliance of oral solid dosage forms demands rigorous analytical testing and quality control to consistently meet quality standards, support product performance, and safeguard patient safety.

In-Process Controls (IPCs)

In-process controls are essential checkpoints during manufacturing to monitor critical quality attributes (CQAs) in real-time and prevent deviations. IPCs are integrated with Process Analytical Technology (PAT) systems to provide continuous monitoring and support real-time release testing (RTRT) approaches.

Finished Product Testing

Once production is complete, finished dosage forms undergo comprehensive testing to confirm compliance with pharmacopeial and regulatory standards.

Stability Testing per ICH Q1A(R2)

Stability studies, as detailed in ICH Q1A(R2), are conducted under accelerated and long-term conditions to establish the product's shelf life and storage conditions. These studies assess physical, chemical, and microbiological stability over time, and therefore are directly related to ensuring efficacy of OSDs over a long period of time.

Analytical Method Validation – ICH Q2(R1)

All analytical methods used for IPC and finished product testing must be validated in accordance with ICH Q2(R1) to generate reliable data, facilitating regulatory submissions, and supporting ongoing process validation and control strategies.

Conclusion

Maintaining quality throughout the product lifecycle of OSDs is not just a regulatory obligation, but essential to ensure their efficacy and compliance. It requires a coordinated approach of using scientifically sound formulation design, incorporating robust manufacturing practices, and diligent quality control.

From selecting appropriate APIs and excipients to validating analytical methods and stability, each stage is integral in delivering safe and effective medicines.

Pharmaceutical manufacturers can further enhance therapeutic outcomes of OSDs by aligning product development with patient-centric principles and regulatory frameworks.