Download Formulation Development Services

Formulation Development
Not all test articles are freely soluble or readily bioavailable. Utilizing a combination
of our formulation expertise and historical knowledge of vehicle suitability, as well
as the close collaboration with our in vivo scientists, Charles River can ensure
an informed lead candidate selection process and a formulation suitable for your
preclinical programs.
Formulation Development
• pH solubility profiling
• Dose suitability
• Compatibility
We offer a comprehensive package of formulation discovery and development
activities in a vast array of formulation types. From preformulation investigations
and screening to formulation validations, stability assessments, compatibility
and assessment of suitability with dosing apparatus, our experience is
unmatched. Extensive global Analytical Chemistry groups utilizing state-of-the-art
instrumentation are available to support our formulation development services.
Successful formulation development requires knowledge of the physicochemical
characteristics of the drug. To achieve this goal, we carry out preformulation
screening prior to formal formulation development experiments.
Since ionizable entities in a drug molecule can significantly alter the solubility
profile and the nature of its interaction with the cell membrane and the target
site, it is important to assess the relative solubility of ionizable drug molecules
at various pH levels. Data derived from such experiments can provide the
basis for optimizing the final formulation, and optimum solubility can often
facilitate higher drug absorption.
pH Solubility Profile of Piroxicam
Absorbance vs. pH of Piroxicam
pH Absorbance (at 353 nm)
Formulation B (400 mg/mL of Piroxicam,
in 15% Labrasol in 0.1 Molar PBS pH 4.5)
Formulation C (400 mg/mL of Piroxicam,
in 15% Labrasol in 0.1 Molar PBS pH 1.2)
0.5
Formulation Types
• Oral
-- Solutions
-- Suspensions
-- Emulsions
-- IV
-- Intramuscular
-- Intraperitoneal
-- Subcutaneous
• Topical
-- Creams
-- Ointments
Formulation A (400 mg/mL of Piroxicam,
in 15% Labrasol in 0.1 Molar PBS pH 6.8)
0.6
• Analytical chemistry
• Parenteral
pH Solubility Profiling
0.7
• Bioavailability enhancement
• Inhalation
-- Nebulizer solutions
-- Powder blends
0.4
0.3
0.2
0.1
0
0
1
3
5
7
9
Time (hours)
11
13
[email protected]
www.criver.com
© 2014, Charles River Laboratories International, Inc.
Dose Suitability
Preclinical formulations, especially those used for oral dosing, are often formulated using high concentrations of test article. As a result,
the physical characteristics of the formulation may not be readily predictable. It is important to assess the stability, ease of preparation,
suitability and other physical characteristics of a formulation during dosing. This information adds confidence and aids in minimizing
complications and delays in future preclinical studies.
Compatibility
Identifying the compatibility (or incompatibility) of a new drug molecule with the appropriate container and dosing apparatus is
essential for developing a good experimental design. The identification and resolution of such issues as early as possible ensures a
successful study with minimal time delays.
Bioavailability Enhancement
Poor drug solubility often correlates with poor bioavailability. The use of cosolvents, solubilizing excipients and biological enhancers
can improve both solubility and drug absorption. However, a critical balance must exist between improving solubility and minimizing
unnecessary side effects. By working closely with our Discovery and Toxicology in vivo scientists, formulations are optimized for
improved results and minimal toxicity of formulation components.
Potential Effect of Formulation Excipients on Bioavailability
Plasma Concentration vs. Time
0.09
O
Plasma concentration (μg/ml)
0.08
CH3
O
N
S
0.07
NH
N
0.06
O
0.05
OH
0.04
0.03
0.02
0.01
0
0
5
10
15
Time (hours)
20
25
Analytical Chemistry Support
The extensive experience and resources available within the Analytical Chemistry groups at Charles River serve as the backbone for
validating and analyzing the produced formulations. It is essential to have reliable and robust analytical methods in the development
stages of any preclinical study. Our Analytical Chemistry groups comprise scientific, technical and support staff with many years of
experience and state-of-the-art instrumentation that can meet all your analytical needs.
[email protected]
www.criver.com
© 2014, Charles River Laboratories International, Inc.