Bioavailability & Solubility
LIPID-BASED EXCIPIENTS – Misconceptions About Lipid-Based Drug Delivery
Rollie Fuller and Ron Permutt provide formulators confidence in using LBDDS as part of formulation development programs, by demonstrating their benefits and key functional mechanisms when used and addressing commonly misrepresented, misinterpreted, and misunderstood LBDDS topics.
BIOAVAILABILITY ENHANCEMENT – Solving Low Solubility Challenges to Optimize Drug Delivery Platforms
David K. Lyon, PhD, discusses how low aqueous solubility NCEs have come to define the innovative pharmaceutical pipelines and how advanced technologies are often required to overcome this issue.
PLATFORM TECHNOLOGY – An Alternative Solution for Peptide Drug Formulation
Michael Neely introduces a unique technology platform and provides examples of how it has solved difficult formulation problems while adding significant commercial value to the resulting drug products.
SPECIAL FEATURE – Solubility & Bioavailability: Difficult Beasts to Tame
Contributor Cindy H. Dubin highlights the services many of these outsourced providers offer to enhance solubility and bioavailability and get their clients’ projects to market faster and cost effectively – while maintaining critical quality attributes.
DELIVERY TECHNOLOGY – NeuroDirect™ Ketamine: Novel, Non-Systemic Topical Therapy for PTSD & Associated Intractable Depression
Ronald Aung-Din, MD, and Chantelle G. Martin, MBChB, present scientific data demonstrating how with NeuroDirect technology, the benefits of psychedelic compounds may be achieved without concern for their potential systemic effects.
FORMULATION FORUM – Changing the Landscape of Nanoparticles for Long-Acting Injectable Drugs
Jim Huang, PhD, and Shaukat Ali, PhD, say recently, there has been continued interest in parenteral NPs with sustained-release characteristics as more drugs discovered are poorly soluble and less bioavailable, and these challenges have led to enormous opportunities and launch of many drug products to market.
WHITEPAPER – Case Study-Improving Bioavailability Using PBPK Modeling & Parallel Formulation Screening
A team of bioavailability experts at Catalent used the in-house bioavailability enhancement platform, OptiForm® Solution Suite, to optimize and develop….
WHITEPAPER – Infographic-Zydis® Orally Disintegrating Tablet (ODT) vs. Standard Tablets (ST)
Catalent’s proprietary Zydis® ODT platform is backed by a large number of clinical studies. This infographic provides a high level summary of studies comparing Zydis ODT against traditional oral tablets…..
FORMULATION FORUM – Sterile & Non-Sterile Formulation Capabilities – A CDMO Perspective
Jim Huang, PhD, and Shaukat Ali, PhD, explain how their company is expanding its footprints in sterile manufacturing to handle innovative molecules and leverage its services to emerging and specialty and biopharma companies requiring cGMP materials for preclinical tox and clinical studies.
DRUG-ELUTING IMPLANTS – Sustained-Release Implants – A Targeted Approach to Drug Delivery
Tom Quinci, MSc, believes oncology requires new treatment modalities that are better for patients, and it is time technologies like drug-eluting implants, offering real, achievable advantages, are more widely considered.
EXCLUSIVE ONLINE CONTENT

Conduit Pharmaceuticals Partners With ClinConnect on Cocrystal Development Program
Collaboration underscores Conduit’s mission to advance promising treatments by developing assets that have already completed Phase 1 trials….

New Collaboration With Stevanato Group to Elevate mRNA Production With Nfinity Platform
Quantoom Biosciences recently announced a new collaboration with Stevanato Group, a leading global provider of drug containment and delivery solutions to the pharmaceutical, biotechnology, and life science industries, with the goal of….

Ascendia Pharmaceuticals Develops Novel Nanoemulsion IV Formulation for Clopidogrel That Received IND Approval
Ascendia Pharmaceuticals CEO Jim Huang, PhD, recently announced Ascendia’s patented Emulsol® nanotechnology has been used to develop a novel nanoemulsion IV formulation for….

Lubrizol Licenses Award-Winning Apisolex™ Excipient to Welton Pharma to Develop a Novel Cancer Therapeutic
The Lubrizol Corporation recently announced the licensing of its novel excipient polymer technology, Apisolex™ excipient, to Welton Pharma (Welton). The license allows….

Celanese & Nanoform Demonstrate Enhanced Drug Delivery Through the Power of Smaller Implants
Celanese and Nanoform Finland Plc recently provided an update on their collaboration to evaluate the synergies between their respective technologies in the field of nanoparticle-enabled drug delivery…..
MARKET NEWS & TRENDS
WEBINARS

WEBINAR – Nanoparticle Suspensions: History, Applications & CMC Aspects
This webinar describes the history, CMC aspects, and potential applications of nanoparticle suspensions (NSs). This drug delivery technology should be considered for crystalline, sparingly water-soluble APIs. The presentation highlights….

WEBINAR – Beyond the Lab: Unleashing the Potential of In Silico Modeling in Drug Product Formulation
In this webinar you will learn how digital chemistry tools facilitate rapid screening of formulation parameters, aiding in the identification of optimal drug delivery systems, excipient selection, and dosage forms….

Where Do We Stand on Poorly Soluble Drugs and Peptides in Oral Delivery?
The Rule of 5 suggests that, for oral bioavailability, a better chance for oral absorption is obtained when the molecules are within the parameters of the Rule of 5’. However, the pharmaceutical industry is achieving oral efficacy with drugs that exceed….

Quotient Sciences: Upcoming Solubility Enhancement & Pediatric Development Webinars
Access our webinars on solubility strategies & pediatric drug development….
WHITE PAPERS

WHITEPAPER – Copolymer Microstructures: Connecting Monomer Sequence Distribution With Biomedical End-Application Performance
To gain insights into advanced copolymer characterization techniques and their impact on drug release in biomedical products, we invite you to explore the latest Corbion white paper…..

WHITEPAPER – Accelerate Preclinical Developments & Improve Oral Bioavailability With Lipid-Based Formulation & Encapsulation Technology Combination
This paper covers the benefits of the LBF and capsules combination in dosage form developments, an efficient technology platform to bring efficient and differentiated products to the market.

WHITEPAPER – Improving API Solubility by Salt & Cocrystal Formation
Ensuring sufficient solubility is critical to the success of small molecule drugs. An active pharmaceutical ingredient (API) must be absorbed by the body and enter the systemic circulation to deliver the desired therapeutic effect. Many APIs,….

WHITEPAPER – Overcoming the Knowledge Gap: Long-Acting Injectables & Implantables
This whitepaper delves into the numerous benefits of long-acting drug delivery systems, including their ability to harness highly potent APIs, streamline development and intellectual property protection, and provide consistent drug release over extended periods.

WHITEPAPER – Enhancing the Solubility of Active Pharmaceutical Ingredients Using Hot Melt Extrusion & Polyvinyl Alcohol
This white paper describes how hot melt extrusion (HME) and a specially-engineered grade of polyvinyl alcohol can be used to increase the solubility of DCS IIb molecules.
Bioavailability and Solubility Challenges
Given that a large number of drugs fail to reach the market due to poor solubility and bioavailability, the industry is seeking various methods to mitigate this challenge while many choose to re-formulate existing product candidates. Either way, the demand for novel bioavailability and solubility enhancement methods has grown significantly. To cater to this increasing demand, many contract manufacturers and technology developers have emerged.
What is Solubility?
Solubility is the ability for a drug to be dissolved in an aqueous medium. Drug solubility is defined as the maximum concentration of a substance that can be completely dissolved in a given solvent at a certain temperature and pressure level.
Solubility of drugs is measured by the amount of solvent needed to dissolve one gram of the drug at a specific temperature. For example, a drug that is very soluble needs less than one part solvent to dissolve one gram of the drug. How soluble a drug is varies widely—a drug that is considered soluble needs 10-30 parts, one that is slightly soluble needs 100-1,000 parts and one that is practically insoluble or insoluble needs more than 10,000 parts. How soluble a drug is depends on the solvent, as well as temperature and pressure.
Since 1975, approximately 60 marketed drugs have leveraged solubilization technologies to enhance oral bioavailability. In the preceding 36 years, from the time the FDA required submission of an NDA in 1938, solubilization technology was virtually unused on a regular basis. Apparently, the disease areas focus, drug discovery methodologies, and the lack of mature solubilization platforms restricted the use prior to the 1970s.
In comparison, the past nearly 4 decades have shown robust growth in the reliance on solubilization platforms, accounting on average for around 9% of all NMEs approved from 1975 through 2022, and more than 10% in the past decade. Some years stand out to validate the need and use of solubilization platforms. For example, in 2005, 20% of NMEs approved used technologies including solid dispersion, lipid, and nanocrystal platforms. The data for the most recent 4-year period (2010-2013) seems to represent a slight decline in growth, but it is still early in the decade, and the data set is relatively small. Based on the trends throughout the past 4 decades and the changing chemical space in drug development, we expect the decade will show additional and significant current growth in use of solubilization technologies once we have visibility into the full 10-year period.
Bioavailability & Solubility Impediments
The biggest impediment in addressing bioavailability issues likely lies with a lack of deep familiarity with enabling technologies. Improving drug bioavailability begins with a thorough evaluation of the API’s physical and chemical properties in relation to solubilization in the dose, but more importantly its dissolution in vivo at the site of absorption.
These technologies, such as nanoparticles, cocrystals, computer-aided prodrug design, and electrospinning, represent innovations aimed at enhancing the solubility of a candidate molecule, particularly in the gastrointestinal tract. Technologies such as electrospinning, deep eutectic solvents, and ionic liquids are upcoming formulation approaches to enhance drug solubility, and as the science matures, and the relative strengths and weaknesses are better understood, we expect to see further application of these innovative approaches. They have shown to be successful for some compounds, and have a place alongside other bioavailability enhancement technologies, where each strategy has its benefits and corresponding liabilities. For them to be successful and widely adopted however, they will also have to provide a compelling benefit compared with other well-understood, and commercially precedented technologies, such as amorphous solid dispersions and lipid-based formulations.
Extreme compounds require either significant amounts of stabilizers to maintain the amorphous state or they are not amenable to common manufacturing technologies with reasonable cost of goods due to their low solubility in organic solvents. These include amorphous solid dispersions using polymethacrylate, cellulose, or povidone-based polymeric carriers, she says. In addition, thermostability of new molecular entities becomes an issue as most new molecules have melting points well above 400°F. Alternative production methods for amorphous solid dispersions can address these issues.