Tablets & Capsules

TC0321

Issue link: https://www.e-digitaleditions.com/i/1349974

Contents of this Issue

Navigation

Page 12 of 59

Tablets & Capsules March/April 2021 11 formulation digestion. The API's kinetic solubility can be studied in both standard media and in media containing products of digestion using fiber optic dissolution. This provides useful information when predicting the in vivo dispersion and digestion performance of the formulation system, allowing the formulator to rank order prototype formulations for subsequent animal or clinical studies. The physical and chemical properties of both the API and the LBF containing the API should be considered in selecting the LBF's delivery method. Since LBFs often rely on the body's digestive process as part of their performance profiles, the API's solubility in the formulation as well as the formulation's degree of digestibility and dispersion can influence the absorption process and should be understood and characterized. In other instances, LBFs are not required to enhance bioavailability but rather just serve as a convenient delivery platform, such as for use with pediatric popula- tions, to provide oxidative protection for sensitive APIs, or to improve the content uniformity of low-dose products. Regardless of the end delivery platform, adequate formu- lation characterization is required to identify and control the formulation's critical attributes as well as enough sta- bility to support its use. In addition, the LBF and delivery platform need to be compatible with each other. After developing the LBF, formulators must consider several factors when selecting a suitable delivery platform, especially for clinical studies. Paramount among these factors are timing and resource needs to match clinical schedules. Ideally, the platform should allow for flexible dosing and be easy to handle and administer at the clinic. Adequate formulation stability is necessary to ensure formulation performance (potency, dispersion, and/or digestibility) over the expected duration of study. Finally, if possible, the delivery method should be reflective of the dosage form that will be deployed for later development stages. Lipid formulation classification system The lipid formulation classification system, shown in Table 1, provides an approach for classifying LBFs based on their composition and predicted in vivo digestion and disper- sion behavior [2]. LBFs containing lipophilic components, such as triglycerides, fatty acids, and mono/diglycerides, are digestible and further dispersible in vivo to micelles and mixed micelles upon digestion. Surfactants with a low hydrophilic-lipophilic balance (HLB) (<12) and a high HLB (>12) can be used to aid in the formulation's dispersion and solubilization. Although not truly lipids, hydrophilic components such PEG 400, PEG 600, propylene glycol, glycerin, water, and ethanol can be added to LBFs when the API solubility favors more polar solvents. Development considerations for lipid-based formulation The first step in LBF development is to achieve a thorough understanding of the API's properties and the clinical deliv- erables. For APIs with bioavailability issues, LBFs in solution are generally preferred; however, dose loading issues may require the LBF to be formulated as a suspension. Solution formulations require solubility studies to identify solvent sys- tems that can dissolve enough API to support the target dose; whereas suspensions require particle size characterization and identification of a suitable rheology profile to prevent sedimentation and allow adequate flow during processing. Once candidate excipients have been identified, compat- ibility studies are performed to ensure that the excipients and API are compatible. Prototype formulations can be prepared based on solubility and compatibility studies and then evaluated using several tools, including disper- sion testing, to compare relative dispersibility in simulated gastric and intestinal fluids. Digestibility can be studied using lipolysis testing to determine the rate and extent of Type I Type II Type IIIA Type IIIB Type IV Composition % Triglycerides or mixed glycerides 100 40-80 40-80 <20 N/A Surfactants (HLB<12) N/A 20-60 N/A N/A 0-20 Surfactants (HLB>12) N/A N/A 20-40 20-50 30-80 Hydrophilic co-solvents N/A N/A 0-40 20-50 0-50 In vivo behavior Appearance upon dispersion Non-dispersing Turbid Clear or almost clear Clear Clear Behavior upon dispersion Poor solvent capacity Solvent capacity unaffected Possible loss of solvent capacity Likely loss of solvent capacity Loss of solvent capacity Digestibility Crucial Not crucial, likely Less likely Not likely Not likely Table 1 Lipid formulation classification system

Articles in this issue

Archives of this issue

view archives of Tablets & Capsules - TC0321