HMM304: Therapeutic Development - Class 10 Flashcards

A comprehensive set of Q&A flashcards covering key concepts from HMM304 Week 4 Class 10 on Therapeutic Development.

What are the two main approaches to drug discovery described in the notes?

Non-targeted drug discovery and target-directed drug discovery.

What stages follow drug discovery in pharmaceutical development?

Pharmaceutical development, pre-clinical development, clinical development, and commercialisation & post-market.

What is a lead compound?

A promising molecule identified for further optimization and testing as a potential drug.

What are the three main types of considerations when a drug company decides to start a project?

Strategic issues, Scientific and technical issues, and Operational issues.

In strategic issues, what is meant by unmet medical need?

A fundamental criterion identifying diseases with poor current treatments and potential for new therapies.

What does 'Market considerations' involve in strategic issues?

Disease prevalence and severity, nature of treatment, improvement over existing therapies, and ability to market the drug.

What does 'Company strategy and pipeline' refer to?

How a company's drug development plan aligns with its existing portfolio, specialization, and pipeline timing.

What does government legislation & policy cover in strategic issues?

Pricing, promotion, registration, advertising rules, and potential government subsidies.

What is 'Scientific opportunity' in scientific/technical issues?

Strength of the scientific hypothesis, availability of techniques/tools, and validity of models/assays.

What does 'Competition' refer to in scientific/technical issues?

First-to-market advantage, better versions, IP protection, and 'competitive intelligence' risk.

What are 'Development hurdles' in scientific/technical issues?

Clinical trial duration and cost, patient recruitment, endpoints, and therapy type implications.

What is the 'Patent situation and freedom to operate' in scientific/technical issues?

Status of patents on required research tools and the ability to use them; licensing/royalties considerations.

What are 'Operational issues' in drug development decisions?

Resources required: staff time, staff expertise, facilities, tools and techniques, and funding.

What happens at the Early selection point in strategic decision points?

Lead compound data is gathered and a decision is made whether development is justified based on profitability potential.

What happens at the 'Decision to develop in man' point?

After pre-clinical data, decide whether to start human clinical trials and whether to produce clinical-grade drug.

What happens at the 'Full development decision point' in strategic decision points?

After Phase I and IIa evidence of safety/efficacy; decide to proceed to larger trials and confirm resources/patent life.

What is the 'Submission decision point' in strategic decision points?

Final decision to apply for registration; ensure all required data; consider potential hold-ups and patent window.

What properties should lead compounds ideally possess?

Selectivity for the target, chemical stability, oral administration potential, favorable pharmacokinetics, and BBB permeability if needed.

What are preformulation studies?

Studies to determine physical and chemical properties of the drug to inform dosage form (stability, solubility, dissolution, particle size, etc.).

What is the key objective of stability testing in preformulation?

To predict long-term stability; estimate shelf-life (usually ~3 years) via stressed-condition testing.

What is the role of solubility in preformulation?

Assess water and lipid solubility, pH-dependent solubility, and possibilities for salt formation or solubility enhancers.

What determines dissolution rate in preformulation studies?

Solubility, molecular weight, and particle size; dissolution rate affects how quickly a drug is released.

What is the significance of particle size and morphology?

Small, uniform particles (< a few μm) facilitate blending into tablets/capsules and influence dissolution and flow.

What are common routes of administration and typical dosage forms?

Oral (tablets, capsules, solutions, suspensions, emulsions); Parenteral (injections); Percutaneous (patches); Inhalation (aerosols); Topical (creams, gels); Rectal/Vaginal (suppositories).

What is an ideal oral drug in terms of formulation considerations?

Water soluble, chemically stable at low pH, permeable GI epithelium, able to access site of action (BBB if needed), and resistant to first-pass metabolism.

What are excipients?

Inert substances added to a formulation to improve manufacturability, stability, disintegration, taste, etc.

What are the advantages and disadvantages of capsules as an oral dosage form?

Advantages: easy to swallow, tasteless, fast dissolution. Disadvantages: shorter shelf-life, moisture sensitivity.

What are specialised formulation delivery systems?

Micelles and Liposomes used to improve solubility, PK, and targeting; micelles solubilize lipophilic drugs; liposomes can protect and direct drugs to tissues.

What is a micelle in drug delivery?

A nano-scale sphere (10–80 nm) formed by amphiphilic molecules with a hydrophobic core that dissolves lipophilic drugs.

What is a liposome?

A phospholipid vesicle that can protect hydrophilic drugs and be surface-modified for targeting; usually injected and not for oral use.

What is sustained release and how is it achieved?

Drug release over extended periods (hours to days); achieved by impermeable coatings or polymer gels.

What is controlled release and how can it be achieved?

Release rate that is controllable or responsive to needs; achieved with temperature-sensitive polymers or pH-triggered systems.

What is the blood-brain barrier and its function?

A barrier that regulates passage of ions, molecules, and drugs from blood to brain; formed by tight junctions, pericytes, and astrocyte end-feet.

What are the main mechanisms to cross the blood-brain barrier?

(1) Lipophilic small molecules, (2) endogenous transporters/shuttles, (3) endogenous endocytosis mechanisms.

What is the role of 'shuttles' in crossing the blood-brain barrier?

Coupling drugs to amino acids or sugars to use transporters that carry them across the barrier.

Why is the patent situation important in drug development?

Patents protect lead compounds/tools and define freedom to operate; licensing or royalties may be required; protects market exclusivity.

What is 'competitive intelligence' in drug development?

Sharing of information (often informal) about competitors that informs strategic decisions and IP posture.