Bioavailability & Solubility
WEBINAR – Hot-Melt Granulation Technology for Lipid-Based Pharmaceuticals
Join our experts Dr. Mandar Kodgule, Dr. Rahul Aware, and Dr. Agnivesh Shrivastava live as they take you through compelling case studies, current trends and developments, and insights on mastering the design of hot-melt granulation process.
SPECIAL FEATURE – Outsourcing Formulation Development & Manufacturing: Understanding Critical Attributes Earlier in Development Leads to a More Robust Drug Product
Contributor Cindy H. Dubin speaks with industry leaders on how drug sponsors and CDMOs are collaborating earlier, and highlights how third-party contractors are navigating material shortages and how the industry is shifting to address different therapeutic targets and molecules, such as mRNA.
EXECUTIVE INTERVIEW – Catalent: Developing & Delivering Billions of Doses of Drugs Every Year
Alessandro Maselli, President and Chief Operating Officer of Catalent, talks about his company’s unique approach to drug development partnerships as he prepares to become the company’s new President and Chief Executive Officer on July 1, 2022.
GLOBAL REPORT – 2021 Global Drug Delivery & Formulation Report: Part 2, Notable Drug Delivery and Formulation Product Approvals and Technologies of 2021
In part 2 of this 3-part series, PharmaCircle, in collaboration with Drug Development & Delivery, focuses on notable drug delivery and formulation product approvals.
EXECUTIVE INTERVIEW – Adare Pharma Solutions: The Journey to Become a Full-Service Provider
Tom Sellig, CEO at Adare Pharma Solutions, discusses his expectations for Adare and how he can leverage his 30-plus years of pharma experience to put Adare in a competitive position to address complex formulation and development challenges.
WHITE PAPER: Selecting In-Vitro Dissolution Methodologies for Amorphous Solid Dispersions
Read about how achieving good in vivo performance is a key attribute for ensuring safety and efficacy of oral solid dosage (OSD) forms intended for systemic delivery.
WHITE PAPER – Poloxamer: A Simple & Powerful Solution for Accelerating Dissolution
This white paper will introduce the concept of dissolution and discuss how poloxamers are a simple yet powerful formulation approach that can enhance dissolution rate, while minimizing resource requirements.
SPECIAL FEATURE – Excipients: Exciting Expansion & Innovation
Contributor Cindy H. Dubin speaks with several companies and presents a unique look at how excipients are being used to support current and future innovative active pharmaceutical ingredients.
FORMULATION FORUM – Oral Formulation Approaches for Different Stages of Clinical Studies
Jim Huang, PhD, says it is of the utmost important task to utilize a phase-appropriate formulation development approach for early and later-stage commercial development of oral dosage forms.
PERMEABILITY STUDIES – Onion Epithelial Membrane as a Model for Predicting Intestinal Absorption of Drugs
Antoine Al-Achi, PhD, Mounika Nangineedi, MS, Chaitali Koli, MS, et al, study 19 drugs with varying partition coefficient, water solubility, and molecular weight values to compare their diffusion through the middle epithelial membrane of onion with that of their Caco-2 cell line.
EXCLUSIVE ONLINE CONTENT

Catalent to Acquire Metrics Contract Services for $475 Million
Catalent, Inc. recently announced it has reached an agreement to acquire Metrics Contract Services (Metrics), a full-service specialty Contract Development and Manufacturing Organization (CDMO) with a facility in….

Starton Therapeutics Reports Positive Results From Phase 1 Study Evaluating Continuous Delivery Lenalidomide
Starton Therapeutics Inc. recently announced positive results from high-level data from its Phase 1 study of STAR-LLD, evaluating the pharmacokinetics (PK) and safety of the company’s continuous delivery….

US Government to Support Expansion of Croda Lipid Systems Capability
Croda International Plc recently announced it has entered into a cooperative agreement with the US government in which the government will provide up to $75 million to expand the….

SPECIAL ROUNDTABLE – Which Trends Will Have the Most Impact on Drug Development in 2022?
Drug Development & Delivery posed this question to life science leaders during a recent roundtable discussion. While their responses are varied, a common theme is that COVID-19 has left a lasting impact on the industry….

CordenPharma Increases xRNA-based Capabilities with a Strategic Investment in LNP Formulation Services at its Caponago Injectable Facility
CordenPharma has recently increased its xRNA capabilities at its sterile injectable facility in Caponago, Italy. The company reports that it is investing over €10M in new Lipid Nanoparticle (LNP) formulation,….
MARKET NEWS & TRENDS
WEBINARS

WEBINAR – Hot-Melt Granulation Technology for Lipid-Based Pharmaceuticals
Join our experts Dr. Mandar Kodgule, Dr. Rahul Aware, and Dr. Agnivesh Shrivastava live as they take you through compelling case studies, current trends and developments, and insights on mastering the design of hot-melt granulation process.

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

WHITE PAPER: Selecting In-Vitro Dissolution Methodologies for Amorphous Solid Dispersions
Read about how achieving good in vivo performance is a key attribute for ensuring safety and efficacy of oral solid dosage (OSD) forms intended for systemic delivery.

WHITE PAPER – Poloxamer: A Simple & Powerful Solution for Accelerating Dissolution
This white paper will introduce the concept of dissolution and discuss how poloxamers are a simple yet powerful formulation approach that can enhance dissolution rate, while minimizing resource requirements.

Outsourcing Drug Development & Production: Technology-Driven Drug Delivery Systems for Small Molecules at Losan Pharma
Due to the increasing demand for drug delivery systems that are able to improve the properties of low soluble, poor permeable, or highly dosed new and existing drug substances, technology-driven CDMOs can offer a wide range of technology platforms to overcome such challenges….
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.