How R&D Helps Pharma Companies Develop Better Drug Delivery Systems

Credo Life Science

Posted on 27th January 2022

A molecule with therapeutic potential is only the beginning of a medicine. Between an API with proven pharmacological activity and a medicine that patients can take reliably, absorb consistently, and benefit from safely lies an often underappreciated scientific discipline: pharmaceutical formulation research and development. Drug delivery R&D is the science that bridges the gap between chemistry and clinical medicine.

In the modern pharmaceutical industry, formulation R&D has evolved from an empirical art into a data-driven, mechanistic science — incorporating polymer chemistry, colloidal science, computational modelling, process engineering, and regulatory strategy. The most impactful advances in drug delivery over the past two decades — sustained-release pellets, nanoparticle drug carriers, solid amorphous dispersions, targeted intestinal delivery — have come not from new molecules but from R&D-driven innovations in how existing and new molecules are formulated and delivered.

Credo Life Sciences invests continuously in pharmaceutical R&D to develop and deliver better drug delivery solutions — particularly for pellet-based multiparticulate systems, taste-masked granules, and modified-release formulations. This blog explores how R&D enables pharmaceutical companies to develop superior drug delivery systems that benefit patients, satisfy regulators, and succeed commercially.

1. R&D Solves the Bioavailability Problem — The Industry's Biggest Challenge

The BCS Classification Crisis

An estimated 40% of currently marketed drugs and up to 70% of new chemical entities in development are classified as BCS Class II (low solubility, high permeability) or BCS Class IV (low solubility, low permeability). These drugs face a fundamental bioavailability challenge: they don't dissolve adequately in gastrointestinal fluids, meaning that even when a patient swallows the prescribed dose, only a fraction of it actually enters the bloodstream.

Without R&D-driven formulation intervention, these drugs would either fail clinical development due to poor and variable exposure, require prohibitively large doses to achieve therapeutic plasma levels, or demonstrate unacceptable food effects that make consistent dosing impossible.

R&D Approaches to Bioavailability Enhancement

Pharmaceutical R&D has developed a portfolio of evidence-based strategies for overcoming poor bioavailability:

Particle Size Reduction and Micronisation

The most straightforward approach — reducing API particle size increases surface area, accelerating dissolution. R&D determines the optimal particle size target (typically D50 3–10 µm for micronised products) and the milling or micronisation technology best suited to the API's physical properties. The development of micronised ciprofloxacin and fenofibrate granules at Credo Life Sciences exemplifies this approach.

Amorphous Solid Dispersions (ASDs)

R&D has established that dispersing a poorly soluble crystalline drug in an amorphous polymer matrix can increase apparent solubility by 10–100 times. The drug exists in a higher-energy amorphous state that dissolves more rapidly than the crystalline form. R&D identifies the optimal polymer (PVP, HPMC-AS, Soluplus), the drug:polymer ratio, the processing technology (hot melt extrusion or spray drying), and the stability conditions — a complex, multi-variable optimisation that requires systematic experimental design.

Nanoparticle Technology

Nanosizing APIs to < 1000 nm (nanocrystals) dramatically increases dissolution rate and, for some drugs, enables absorption through new pathways. R&D develops the stabiliser system (surfactants, polymers) that prevents nanoparticle aggregation, optimises the milling process (wet media milling, high-pressure homogenisation), and validates the downstream processing steps to incorporate nanoparticles into solid dosage forms.

2. R&D Enables Modified-Release Drug Delivery — Transforming How Drugs Work

From Three-Times-Daily to Once-Daily: The Adherence Revolution

One of the most impactful contributions of pharmaceutical R&D to patient care has been the development of modified-release drug delivery systems — formulations that control the rate, timing, and location of drug release after administration. By reducing dosing frequency from three or four times daily to once daily, R&D-driven modified-release formulations have transformed adherence in chronic disease management.

Selection of the appropriate drug delivery mechanism (diffusion-controlled membrane vs. erosion-controlled matrix vs. osmotic pump)
Polymer system selection and characterisation (ethyl cellulose, Eudragit RS/RL, HPMC)
Quantitative formulation optimisation using Design of Experiments (DoE) methodology
In vitro–in vivo correlation (IVIVC) development — establishing mathematical relationships between dissolution profiles and plasma concentration curves
Scale-up from laboratory to pilot to commercial scale with preservation of release performance

The development of a sustained-release pellet system involves R&D decisions at multiple levels:

Designing for the Right Release Profile

Not all modified-release systems are created equal. R&D determines the optimal release profile for a specific drug based on its pharmacokinetic properties, therapeutic window, and disease management requirements. Some drugs benefit from near-zero-order release (constant rate throughout the dosing interval); others require a biphasic profile (rapid initial release followed by sustained delivery); still others need site-specific release (enteric coating for duodenal or ileal release targeting).

At Credo Life Sciences, our formulation R&D team develops release profiles using in vitro dissolution modelling, pharmacokinetic simulation (using tools such as GastroPlus), and iterative formulation adjustment — ensuring that the developed SR or EC pellet system delivers the intended clinical pharmacokinetic profile.

3. R&D Solves Palatability Challenges — Making Medicines Patients Will Actually Take

The Taste Masking R&D Process

Bitterness quantification: using e-tongue (electronic taste sensor) analysis to objectively measure the bitterness intensity of the uncoated API and set a quantitative target for taste masking efficacy
Polymer system screening: evaluating candidate taste-masking polymers (Eudragit E PO, Eudragit RS, ethyl cellulose, ion-exchange resins) for their ability to suppress dissolution at salivary pH
Coating process development: optimising spray rate, air temperature, coating weight gain, and plasticiser level for complete and uniform coating of each granule
In vitro taste masking validation: dissolution testing at pH 6.8 (simulated saliva) with specification NMT 5% in 30 seconds
Bioequivalence confirmation: dissolution testing at gastric and intestinal pH to confirm that taste masking does not reduce drug bioavailability
Taste panel assessment: sensory evaluation by trained adult volunteers to confirm acceptability

This systematic R&D programme — conducted by Credo Life Sciences' formulation team for ciprofloxacin, azithromycin, and clarithromycin taste-masked granules — ensures that the developed product is both scientifically validated and clinically effective.

4. R&D Generates the Regulatory Evidence Base — Essential for Market Approval

Quality by Design (QbD) — R&D's Regulatory Framework

Define the Target Product Profile (TPP): clinical and quality attributes the product must achieve
Identify Critical Quality Attributes (CQAs): parameters most important to product performance and patient safety
Map Critical Material Attributes (CMAs) and Critical Process Parameters (CPPs): inputs that affect CQAs
Establish a Design Space: the multivariate range of CMAs and CPPs within which the product meets all CQAs
Implement a Control Strategy: manufacturing controls that ensure the design space is consistently achieved

For pellet-based formulations, this QbD framework connects formulation R&D data directly to manufacturing process controls and regulatory submissions — creating a scientifically rigorous, regulatorily coherent pathway from development to approval.

Analytical Method Development — The Measurement Foundation of Drug Delivery R&D

Every drug delivery R&D programme requires validated analytical methods to measure what has been formulated. For modified-release pellets, this includes:

Stability-indicating HPLC assay methods capable of separating API from degradation products
Dissolution methods that discriminate between formulations and correlate to in vivo performance
Particle size analysis methods validated for the specific particle size range and matrix
Residual solvent and heavy metals analysis for relevant excipients

Credo Life Sciences' QC laboratory provides in-house analytical method development and ICH Q2(R1) validation for all drug delivery projects — ensuring that the analytical infrastructure required for regulatory submission is built into the development programme from the start.

5. R&D Partnerships: How CDMOs Accelerate Drug Delivery Development

The CDMO R&D Advantage

Established drug delivery platforms: a CDMO with an existing validated SR pellet or EC pellet platform can compress development from 18 months to 6–8 months for a product fitting the platform
Equipment continuity: when the same equipment used for development is used for commercial manufacturing, scale-up risk is dramatically reduced
Regulatory experience: CDMOs that have supported multiple successful ANDA and dossier submissions have proven documentation systems that reduce first-cycle approval rejection risk
Risk-sharing models: technology transfer, milestone-based fee structures, and profit-sharing arrangements allow pharmaceutical companies to access CDMO R&D expertise without high upfront investment

Credo Life Sciences R&D Partnership Model

Credo Life Sciences engages pharmaceutical partners through a structured drug delivery R&D programme:

Feasibility assessment (2–4 weeks): API characterisation, target product profile review, and platform selection
Formulation development (4–16 weeks): prototype development, DoE optimisation, in vitro evaluation
Analytical development (concurrent): method development, partial validation, stability initiation
Scale-up and exhibit batch manufacture: pilot to commercial scale
Regulatory documentation: BMRs, analytical method validation reports, stability reports, CMC section preparation

This structured programme, supported by Credo's WHO-GMP manufacturing facility, ensures that R&D outputs translate directly into commercially manufactured, regulatorily approved products — not laboratory findings that require a separate, disconnected manufacturing development programme.

Pharmaceutical R&D is the engine that transforms molecules into medicines. For drug delivery systems — especially sophisticated multiparticulate technologies including IR pellets, SR pellets, EC pellets, and taste-masked granules — R&D is not a preliminary step before manufacturing; it is an integrated scientific programme that defines every aspect of the product from patient experience to regulatory approval.

Pharmaceutical companies that invest in, or partner with organisations that invest in, rigorous formulation R&D consistently achieve better clinical outcomes, faster regulatory approvals, and more commercially successful products. Credo Life Sciences' commitment to pharmaceutical R&D — in formulation science, process development, analytical chemistry, and regulatory strategy — is the foundation of every pellet and granule product we develop and manufacture for our partners worldwide. Contact Credo Life Sciences to explore how our drug delivery R&D capabilities can accelerate your next pellet or granule formulation project.