Phospholipids as functional excipient in solid oral dosage forms
Phospholipids have gained importance as formulation excipients due to their physicochemical diversity, biocompatibility, and capacity to enhance oral bioavailability of poorly water-soluble drugs.1)2) The main techniques for transforming liquid or semi-solid lipid formulations into solid-based particles or granules are spray-cooling, spray-drying, adsorption onto solid carriers, melt granulation, melt extrusion, supercritical fluid-based methods and high pressure homogenization.3) However, few studies have evaluated conventional dosage forms such as tablets containing phospholipids. Studies on incorporation of phospholipids into solid oral dosage forms such as tablets and pellets are rare.
Tableting involves several energy intensive processes, which could be a challenge for processing of phospholipids due to their “waxy” nature. Furthermore, powder properties such as the flowability and density of phospholipids and their blends with common excipients are important factors for their potential use in this conventional dosage form. The functionality of phospholipids within solid oral dosage forms needs to be evaluated to explore the advantages of adding phospholipids as a formulation component. Finally, phospholipids may also be considered as active ingredients by themselves, since their beneficial effect in relation to different illnesses and symptoms, e.g. coronary heart disease, inflammation or cancer has been long time discussed in the literature,4) thus the feasibility to prepare solid dosage forms containing different phospholipids is crucial for patient compliance.
This project, therefore, covers explorative studies on the incorporation of phospholipids into solid oral dosage forms such as tablets and alternatively multiparticulates such as pellets. Additionally, studies to investigate potential advantages of phospholipids as extended release excipients for various model drugs are included.
Benefit for the community
The community benefits from a viable replacement option for synthetic, non-degradable excipients using biodegradable excipients from natural sources in oral dosage forms applicable to a wide range of patient treatments.
Extensive work on the processability of lecithin with different phospholipid fractions into solid dosage forms was performed. Methods to obtain free flowing powders (i.e. granules) with up to 60% unsaturated phospholipids and, consequently, tablets with reasonable hardness, were described.
Furthermore, hydrogenated soybean phosphatidylcholine (HSPC) was evaluated as insoluble matrix former. Direct compression of binary blends of model drugs and phospholipid was used to establish clear cause-effect relationships and to evaluate the general applicability of HSPC as release retarding matrix-former. The pH-dependent behavior of HSPC matrix was elucidated and formulation parameters to assess it were suggested.
Finally, the feasibility to process HSPC by hot-melt extrusion due to its liquid crystalline nature was evaluated for the first time. Non-eroding extrudates with up to 70% drug loadings were prepared at temperatures below their melting points, resulting in crystalline dispersions. The mechanical robustness of the extrudates was attributed to the formed skin-core structure and was identified as the main reason for the major release controlling potential of extruded matrices compared to compressed ones.
Lipid – An emerging platform for oral delivery of drugs with poor bioavailability
Eur. J. Pharm. Biopharm. 73, 1-15
Phospholipids and Lipid-Based Formulations in Oral Drug Delivery
Pharm. Res. 27, 1469-1486
Approaches for the development of solid and semi-solid lipid-based formulations
Adv. Drug Del. Rev. 60, 734-746
Health effects of dietary phospholipids
Lipids Health Dis. 11, 3
Saturated phosphatidylcholine as matrix former for oral extended release dosage forms
Eur. J. Pharm. Sci. 108, 86-92
Evaluation of Hydrogenated Soybean Phosphatidylcholine Matrices Prepared by Hot Melt Extrusion for Oral Controlled Delivery of Water-Soluble Drugs
AAPS PharmSciTech 20, 159