Simple, immediate release (IR) and once-a-day (QD) formula­tions are desired not only by the patient for rapid onset and im­proved compliance, but also by the pharmaceutical industry due to ease of development and cost benefits. However, many small molecules in today’s pipelines have sub-optimal properties for QD IR formulations. 

Challenges, including poor solubility or per­meability, can lead to reduced absorption (input in the body) or high clearance (output from the body) that causes a short dura­tion of therapeutic effect. This results in more frequent dosing reg­imens, which may not be suitable for patient compliance. 

Another challenge comes from the significant peaks and troughs in circu­lating drug concentrations. Using IR formulations, the drug im­mediately enters the bloodstream, and if dosing is not optimized, this could lead to side effects for the patient and variation in ther­apeutic efficacy. For IR formulations that require more than once-a-day dos­ing, a modified release (MR) formulation, which delivers the drug to the lower GI tract over a sustained period, can be a better choice to achieve the desired therapeutic effects.

The following will discuss the opportunities and challenges when transitioning from an IR to MR formulation. It will review the therapeutic ben­efits and challenges associated with MR formulations, GI physi­ology environments and API physicochemical properties, technology choices, and how drug developers can achieve trans­lation success.

To continue reading this article featuring Vanessa Zann, Executive Drug Development Consultant, visit the Drug Development & Delivery website. 

Following approval in November from the UK Medicinal and Healthcare Products Regulatory Agency (MHRA), Nanomerics Ltd., a private speciality pharmaceutical company, and Quotient Sciences have commenced dosing the first volunteers for the Phase I trial of OC134.

OC134 is an eye drop medicine candidate indicated for the topical treatment of moderate to severe allergic conjunctivitis, a condition for which a suitable non-steroidal topical ocular treatment, does not currently exist.

The clinical testing of Nanomerics’ eye drop assets is being done by Quotient Sciences - Nottingham, UK.

Dr Nand Singh, Medical Director at Quotiexnt Sciences commented, “We are excited to begin clinical testing at our Nottingham, UK clinic for Nanomerics’ OC134 Phase 1 Sunlight trial. This marks an important step forward in developing advanced treatments for moderate to severe conjunctivitis.”  

Continue reading the announcement from Nanomerics 

At the 26th North American ISSX and 39th JSSX Meeting in September 2024, Quotient Sciences presented three posters showcasing significant advancements in the pharmacokinetics and metabolism research of acoziborole. 

Acoziborole is a potentially transformative investigational treatment for Human African trypanosomiasis (HAT), commonly known as sleeping sickness. This is an illness caused by protozoan parasites transmitted by infected tsetse flies. It is endemic in sub-Saharan Africa and without treatment is typically fatal. Most people impacted by HAT live in rural areas and depend on agriculture, fishing, animal husbandry, or hunting. 

Continue reading to see how Quotient Sciences supported the radiosynthesis and GMP repurification of 14C drug substance of oxaborole-6 carboxamide, followed by the ADME studies in healthy subjects. 

Poster 1: Mass Balance Recovery, Absorption, Metabolism, and Excretion of [14C]Acoziborole – Preparation of GMP [14C]Acoziborole Drug Substance 

This poster outlines the radiolabelling and purification process for [14C]acoziborole, a radiolabelled drug produced under GMP standards to support human metabolism studies. It outlines the synthesis process, including the initial non-GMP preparation from barium [14C]carbonate and the subsequent GMP repurification conducted in a dedicated radiosynthesis laboratory. 

This process ensures that the final product meets regulatory standards through thorough quality control and assurance measures. As a result of the careful synthesis and purification, the final product is a GMP-compliant [14C]acoziborole, now ready for use in human studies.

Access the full poster for more on the process and outcomes. 

Poster 2: A Single Dose Study to Assess the Mass Balance Recovery, Absorption, Metabolism, and Excretion of [14C]Acoziborole in Healthy Male Subjects 

A Phase 1 open-label clinical study was conducted to examine the mass balance, pharmacokinetics, metabolism, and excretion (ADME) of acoziborole. The study involved six healthy male participants and provided key insights into how the drug is processed in the body. 

This study, funded and sponsored by DNDi in Geneva, Switzerland, was conducted by Quotient Sciences at our integrated drug product formulation development, drug product manufacturing, and clinical pharmacology facility in Nottingham, UK.

In this study, participants received a single oral dose of 960 mg [14C]-acoziborole. Over the next 120 days, researchers collected samples of blood, plasma, urine, and faeces to evaluate the drug's absorption and elimination. However, the study encountered challenges due to the COVID-19 pandemic, which restricted urine collections to just 16 days post-dose.  

Key findings indicate that acoziborole was well tolerated, demonstrating good absorption with predominantly slow biliary-faecal elimination and minimal urinary excretion. Notably, acoziborole was the most abundant circulating component in plasma. This poster describes the mass balance and clinical safety assessments from the human ADME study.  

Download the full poster to explore the detailed methodology and findings. 

Poster 3: Investigation of the Metabolite Profile of Acoziborole in Plasma, Urine, and Fecal Homogenate Samples Using UPLC-MS Fractionation Followed by AMS Analysis 

This poster focuses on the analysis of metabolites following a human ADME study that used a microdose of [14C]-acoziborole. To accurately assess the metabolites present at such low doses, Accelerator Mass Spectrometry (AMS) was employed. The research involved preparing pools of plasma, urine, and faeces homogenates to investigate the metabolites. 

Using a sophisticated analysis method called data-dependent acquisition, the study detected metabolites in these samples and assigned them to specific fractions where their activity exceeded baseline levels, based on their molecular mass. This research contributes to our understanding of the drug’s metabolic pathway, its safety profile in humans, and its potential as an effective treatment for HAT.

For a breakdown of the methodology and results, access the full poster. 

Quotient Sciences has been recognized as a winner of the 2024 Fierce CRO Awards category for "Innovative Solutions in Drug Development."

The Fierce CRO Awards celebrate exceptional achievements and innovations by Contract Research Organizations (CROs). These awards recognize CROs that have demonstrated outstanding performance, innovation, and leadership in delivering high-quality research and development services. 

Entries in the 2024 Fierce CRO Awards were judged on the ability of the applicant to demonstrate innovation, impact, measurable outcomes, sustainability, scalability, ethical and regulatory adherence. This includes:

• The level of creativity and effectiveness in advancing research and development services within the life sciences sector
• Evidence of tangible results and improvements, such as successful trials, enhanced data quality, or improved client satisfaction
• The potential for long-term impact and the ability to apply successful practices on a broader scale
• Commitment to maintaining high ethical standards and complying with relevant regulations

The company was recognized for its submission to the Innovative Solutions in Drug Development category, showcasing the impact of the Translational Pharmaceutics platform for integrated drug development to programs with Evecxia Therapeutics on EVX-101 and with Ensysce Biosciences on PF614-MPAR.

Translational Pharmaceutics® integrates real-time cGMP drug product manufacturing (including oral solid dosage forms, such as tablets and capsules), clinical testing, project management, data sciences, and related capabilities needed for a Phase I clinical trial with healthy volunteers. Each year, Quotient Sciences are consistently a leading provider of Phase I clinical trials in the UK site and in US via our global network.

Combining services and expertise as both a CDMO and CRO into one program makes it easy for clients to complete their programs, while benefitting from a single project manager for the entire process with oversight of a cross-functional project team. 

"I'm proud of our teams for this accomplishment," commented Thierry Van Nieuwenhove, CEO, Quotient Sciences. "Giving our customers direct lines of communication to subject matter experts and a more integrated way to complete drug programs are two things that consistently set us apart from competitors. On each and every project that Quotient Sciences partner, we will gather a team of drug development specialists, worldwide recognized, to support our customers in every step of their development, from design to proof of concept."