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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 The molecules are withdrawn at various stages of discovery and development process for reasons such as poor ADME properties, lack of efficacy and safety reasons.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.


Flow chart for showing various formulation/drug delivery solutions for drug attrition during discovery and development.
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f0020: Flow chart for showing various formulation/drug delivery solutions for drug attrition during discovery and development.

Mentions: Minocycline is oral antibacterial drug used to treat variety of infection and commonly prescribed for treatment of acne. The immediate release formulations reported to produce vestibular adverse effects. The extended release formulation of minocycline was tested clinically for treatment of acne and incidence of vestibular side effects. The extended release formulation at 1 mg/kg body weight significantly reduced the number of inflammatory lesions. The reports of vestibular adverse events were comparable to placebo group127. The formulation was found effective in treating acne without significant adverse effects. Similarly, extended release formulation of niacin (NIASPAN®) was reported to provide consistent and desired plasma level required for pharmacological activity and incidence of liver toxicity were reported to be significantly less than sustained release formulations128. The extended release formulation was found efficacious in treating hyperlipidemia and liver related adverse effects were comparable to placebo group128. The delayed release formulations of fenofibric acid was found effective in treating hyperlipidemia alone or in combination with statins129. Another nice example of formulation playing important role in developability of molecule is didanosine formulation. Initially, didanosine was administered as solution/suspension with antacids/buffered tablet. The didanosine was believed to degrade in acidic pH conditions of gastric fluid and cause side effects. Buffered formulations were reported to reduce the toxicity of molecule. Recently, enteric coated formulation has been approved and has displayed comparable pharmacokinetic profile with improved tolerability130. Briefly, these examples clearly demonstrate that timed release formulations have greater potential in salvaging molecules with toxicity/safety concerns. Overall, summary of formulations/drug delivery systems contributing to improved clinical applications or overcoming developmental barriers of drug molecules is shown in Fig. 4.


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)

Flow chart for showing various formulation/drug delivery solutions for drug attrition during discovery and development.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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

f0020: Flow chart for showing various formulation/drug delivery solutions for drug attrition during discovery and development.
Mentions: Minocycline is oral antibacterial drug used to treat variety of infection and commonly prescribed for treatment of acne. The immediate release formulations reported to produce vestibular adverse effects. The extended release formulation of minocycline was tested clinically for treatment of acne and incidence of vestibular side effects. The extended release formulation at 1 mg/kg body weight significantly reduced the number of inflammatory lesions. The reports of vestibular adverse events were comparable to placebo group127. The formulation was found effective in treating acne without significant adverse effects. Similarly, extended release formulation of niacin (NIASPAN®) was reported to provide consistent and desired plasma level required for pharmacological activity and incidence of liver toxicity were reported to be significantly less than sustained release formulations128. The extended release formulation was found efficacious in treating hyperlipidemia and liver related adverse effects were comparable to placebo group128. The delayed release formulations of fenofibric acid was found effective in treating hyperlipidemia alone or in combination with statins129. Another nice example of formulation playing important role in developability of molecule is didanosine formulation. Initially, didanosine was administered as solution/suspension with antacids/buffered tablet. The didanosine was believed to degrade in acidic pH conditions of gastric fluid and cause side effects. Buffered formulations were reported to reduce the toxicity of molecule. Recently, enteric coated formulation has been approved and has displayed comparable pharmacokinetic profile with improved tolerability130. Briefly, these examples clearly demonstrate that timed release formulations have greater potential in salvaging molecules with toxicity/safety concerns. Overall, summary of formulations/drug delivery systems contributing to improved clinical applications or overcoming developmental barriers of drug molecules is shown in Fig. 4.

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.