Formulating products that have the right composition, viscosity, texture and stability, and which may also be safe and effective, is both a science and an art. This requires having access to appropriate techniques and skills, state-of-the-art equipment, process scientists and engineers who have a thorough understanding of Quality by Design (QbD) principles and methods for characterizing products and processes.
Expertise in analytical testing, validation and quality control is also essential. The preparation of a semi-solid dosage form – from formulation and development to scale-up, commercial manufacturing and packaging – should ideally take place under one roof in a contiguous end-to-end workflow. tip to avoid unnecessary equipment and process changes. Without proper precautions, knowledge gaps can occur and important details can be overlooked when a product is transferred from one site to another.
It is important for a CDMO to understand the market they serve and, in the dermatology field, this means the demand for topical agents in a wide range of indications. It is also essential to keep abreast of the latest scientific and technological advances.
Above all, when it comes to developing and delivering a safe and effective product in a cost effective and timely manner, simplicity matters. At Cambrex, quality comes first, and the same quality expectations also apply to prescription and over-the-counter topical products. Cambrex’s one-stop-shop approach ensures that all aspects of product formulation, analysis and manufacturing can be performed on-site, by trained scientists and engineers, using the same state-of-the-art equipment and the same validated methods. This applies to new products and technology transfers, thus avoiding the problems that can arise when transferring existing methods and processes to a new site. Cambrex provides end-to-end formulation and manufacturing at its Mirabel plant (Quebec, Canada) with the production of sterile ointments carried out at its Whippany site (NJ, United States).
Optimize development and scale
When initiating the development of a prescription dermatology product, formulation selection is at the top of the list. The choice between an ointment, gel or cream will depend on several factors, including the following: the indication, the area to be treated, how the medicine will be applied, the physicochemical properties of the API, whether the API works on the surface of the skin or needs to be absorbed through the skin, potential incompatibility issues between ingredients and stability factors.
The texture and quality of any topical formulation is critical. The main characteristics targeted are a non-grainy texture, soft to the touch, pleasant smell, non-irritating and easy to apply. To achieve these properties, development work should focus on optimizing five key physical characteristics of the product formulation:
• Particle distribution
• Spreadability (ease of application vs tendency to run)
• Need for surfactants
Proper equipment is essential. This includes mixers, emulsifiers, grinders and agitators. Controlling the temperature, and in particular the cooling rate when mixing the oil and water phases, is crucial. Process design studies will identify the ideal temperature ranges for each stage of the process, and precise monitoring will ensure that temperatures remain at the sweet spot needed for proper mixing at all times.
Heated and cooled jacketed mixing tanks are required to ensure precise temperature control. Proper mixing and temperature control technology is also important when adding gelling agents and APIs to ensure proper particle distribution and to maintain formulation stability and uniformity. The wide range of mixing equipment, temperature-controlled tanks and lauter tuns available in Cambrex’s development and manufacturing suites allows for experimentation and optimization of process design and scale-up to commercial cGMP production.
To ensure that semi-solid dosage forms remain stable and retain the desired physicochemical characteristics over time, tests should be performed to assess oil and water phase separation, color or pH changes, crystallization, changes in particle distribution and product degradation. Cambrex offers a full range of chemical tests needed to characterize and monitor the properties of products in development.
In vitro release assays to demonstrate bioequivalence
The U.S. Food and Drug Administration’s Scale-Up and Post Approval Change Semi-Solids (SUPAC-SS) Task Force has issued recommendations for component and compositional changes and in vitro release testing ( IVRT) for bioequivalence to support any change in formulation, manufacturing (processes and equipment), scale-up/scale-down and/or manufacturing site of a semi-solid topical preparation on non-sterile prescription.
Cambrex can support Q1-3 testing as follows:
• Q1 = the products have the same components
• Q2 = the products have the same components in the same concentrations
• Q3 = the products have the same components in the same concentrations with the same material arrangement (microstructure) and the same rate of permeability
Cambrex performs validated IVRT on product development batches and also offers a range of bioassays to demonstrate product potency, where applicable.
Bioburden and microbial tests
Products must also be tested for microbial load to demonstrate that they do not contain microbial contaminants. Cambrex’s microbiology laboratory has the capacity to perform all necessary microbial testing. Depending on the product, the range of tests may include the following:
• Microbial Limit Testing – to determine if a product meets compendial specifications; targets specific undesirable organisms and assesses their presence or absence in a product
• Microbial count – quantifies the total count of aerobic organisms and determines a total count of yeasts and molds combined
• Microbial bioassay – measures the potency of a biologically active substance (eg an antibiotic)
• Bioburden test – measures the population of viable microorganisms in a product
• Preservative Effectiveness Test/Antimicrobial Effectiveness Test (AET): assesses the effectiveness of antimicrobial preservatives added to the formula
Simplify technology and site transfer
Technology transfer presents challenges when it comes to producing semi-solid dosage forms due to the difficulty of achieving the exact same texture, viscosity and consistency of a product when changing even a single method or piece of equipment in the production process.
Site transfer requires a company to return to the very early stages of product formulation and development, including sourcing and analyzing raw materials, characterizing critical product attributes, and defining the product space. process design. Even the smallest details can have a big impact on the end result, especially when it comes to the sensory characteristics and bioequivalence of a topical product.
The complexities and risks associated with the development and manufacture of semi-solid dosage forms, whether prescription dermatological drugs or over-the-counter topical products, can be managed with the knowledge, experience and support from a full-service CDMO partner.
Cambrex has proven expertise in manufacturing a wide range of formulation types in scales from 10kg to 900kg. With commercial semi-solid products on the market, Cambrex offers its customers the technical capabilities, experts and cutting-edge technology necessary to seamlessly transition a topical product from development to clinical material to full-scale commercial supply. .
Simplicity matters when it comes to early stage product formulation; high-quality, consistent and cost-effective scaling, manufacturing and packaging, and comprehensive analytical testing and quality control. Cambrex’s one-stop shop enables the development and manufacture of prescription and over-the-counter products, whether sterile or non-sterile, in one place in a streamlined, cost-effective workflow. This increases confidence, reduces the risk of uncertain results that can result from changing equipment and processes, and can even speed the path to regulatory approval.
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