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Can formulation and drug delivery reduce attrition during drug discovery and development-review of feasibility, benefits and challenges.

Basavaraj S, Betageri GV - Acta Pharm Sin B (2014)

Bottom Line: Drug discovery and development has become longer and costlier process.The fear of failure and stringent regulatory review process is driving pharmaceutical companies towards "me too" drugs and improved generics (505(b) (2)) fillings.The formulation and drug delivery technologies are suitable for addressing various issues contributing to attrition are discussed in detail.

View Article: PubMed Central - PubMed

Affiliation: Western Centre for Drug Development, Western University of Health Sciences, Pomona, CA 91766, USA.

ABSTRACT
Drug discovery and development has become longer and costlier process. The fear of failure and stringent regulatory review process is driving pharmaceutical companies towards "me too" drugs and improved generics (505(b) (2)) fillings. The discontinuance of molecules at late stage clinical trials is common these years. The molecules are withdrawn at various stages of discovery and development process for reasons such as poor ADME properties, lack of efficacy and safety reasons. Hence this review focuses on possible applications of formulation and drug delivery to salvage molecules and improve the drugability. The formulation and drug delivery technologies are suitable for addressing various issues contributing to attrition are discussed in detail.

No MeSH data available.


Representative scheme for drug discovery and development with reasons for attrition at each stage.
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f0005: Representative scheme for drug discovery and development with reasons for attrition at each stage.

Mentions: The discovery and development of drug involves various stages. The flow chart in Fig. 1 depicts simplified drug discovery and development process19. The hunt for new drug starts with selecting disease and identification of target. The molecules from synthesis or biological origin would normally be screened for in vitro biological activity. The selected molecules then move to further preclinical testing such as in vivo activity in animal models, in vitro metabolism and pharmacokinetic profiling in animals. During this stage molecules will also be tested for physicochemical properties such solubility, ionization and partition behavior. The molecules with desired activity, ADME and physicochemical properties will undergo stringent safety and toxicity testing before they enter clinical testing. The physicochemical parameters coupled with ADME testing will assist in determining drugability of molecules. The biopharmaceutics classification system (BCS) groups molecules into four classes based on solubility and permeability as shown in Fig. 220. The molecules belonging to Class I are believed to more development friendly as they possess desired characteristics which make them more drugable. The molecules belonging to Classes II–IV will have problems associated with either solubility and/or permeability. Lipinski's rule of five also provides useful information on biopharmaceutical behavior of molecules based on molecular weight, H bond donors/acceptors and log P values21. The molecules which lack desired ADME profile will fail to elicit pharmacological activity in vivo. The importance of early ADME prediction and profiling has been reported in the literature and early ADME profiling found to improve output of discovery22. The many hits during discovery fail to become lead candidate for clinical development due to poor ADME properties. The formulation approaches that can improve ADME profile of molecule amenable for further development are discussed here.


Can formulation and drug delivery reduce attrition during drug discovery and development-review of feasibility, benefits and challenges.

Basavaraj S, Betageri GV - Acta Pharm Sin B (2014)

Representative scheme for drug discovery and development with reasons for attrition at each stage.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590717&req=5

f0005: Representative scheme for drug discovery and development with reasons for attrition at each stage.
Mentions: The discovery and development of drug involves various stages. The flow chart in Fig. 1 depicts simplified drug discovery and development process19. The hunt for new drug starts with selecting disease and identification of target. The molecules from synthesis or biological origin would normally be screened for in vitro biological activity. The selected molecules then move to further preclinical testing such as in vivo activity in animal models, in vitro metabolism and pharmacokinetic profiling in animals. During this stage molecules will also be tested for physicochemical properties such solubility, ionization and partition behavior. The molecules with desired activity, ADME and physicochemical properties will undergo stringent safety and toxicity testing before they enter clinical testing. The physicochemical parameters coupled with ADME testing will assist in determining drugability of molecules. The biopharmaceutics classification system (BCS) groups molecules into four classes based on solubility and permeability as shown in Fig. 220. The molecules belonging to Class I are believed to more development friendly as they possess desired characteristics which make them more drugable. The molecules belonging to Classes II–IV will have problems associated with either solubility and/or permeability. Lipinski's rule of five also provides useful information on biopharmaceutical behavior of molecules based on molecular weight, H bond donors/acceptors and log P values21. The molecules which lack desired ADME profile will fail to elicit pharmacological activity in vivo. The importance of early ADME prediction and profiling has been reported in the literature and early ADME profiling found to improve output of discovery22. The many hits during discovery fail to become lead candidate for clinical development due to poor ADME properties. The formulation approaches that can improve ADME profile of molecule amenable for further development are discussed here.

Bottom Line: Drug discovery and development has become longer and costlier process.The fear of failure and stringent regulatory review process is driving pharmaceutical companies towards "me too" drugs and improved generics (505(b) (2)) fillings.The formulation and drug delivery technologies are suitable for addressing various issues contributing to attrition are discussed in detail.

View Article: PubMed Central - PubMed

Affiliation: Western Centre for Drug Development, Western University of Health Sciences, Pomona, CA 91766, USA.

ABSTRACT
Drug discovery and development has become longer and costlier process. The fear of failure and stringent regulatory review process is driving pharmaceutical companies towards "me too" drugs and improved generics (505(b) (2)) fillings. The discontinuance of molecules at late stage clinical trials is common these years. The molecules are withdrawn at various stages of discovery and development process for reasons such as poor ADME properties, lack of efficacy and safety reasons. Hence this review focuses on possible applications of formulation and drug delivery to salvage molecules and improve the drugability. The formulation and drug delivery technologies are suitable for addressing various issues contributing to attrition are discussed in detail.

No MeSH data available.