Lec 11- MR intro Flashcards
1
Q
Modified- release systems
Runnign order for lecture series
A
- Pharmaceutical market and drug delivery systems development
- Rationale for Modified Release products
- Role of polymers
- Design options and mechanism
- Zero order, First-order, root t
- Types of MR products
- Reservoir, matrix, swelling, osmotic
- Timed release, rapidly dissolving products
- Problem solving
2
Q
Modified-release Systems (MR) &
Nomenclature
A
- Controlled release systems (CR)
- Extended Release (ER) or (XL) or Sustained release systems (zero order release profile)
- Long-acting systems (LA)
- Slow or sustained release systems (SR)
- Slow acting systems (SA)
- Delayed release DR e.g. Enteric Coated (EC)
- No release for a small period of time before immediate release profile (rapid increase in concentration)
- Therapeutic delivery systems (TDS)
- Transdermal Therapeutic Systems (TTS)
- Rapid Action
- Fast dissolving preparations e.g. ODTs (Zydis®)
- Limit time for drug disintegration (must disintegrate within 30) dissolution then occurs faster
- Even faster for buccal absorption’s (avoid 1st pass metabolism)
3
Q
Global Pharmaceutical Market
A
- Global pharmaceutical market
- $837 billion
- Pharmaceutical growth worldwide was driven by
- Increased longevity of populations
- Rising wealth
- Innovative new products
- New applications for existing products
4
Q
Global Drug Delivery Market
A
- The global drug delivery market
- $26bn in 2000 to approximately $60bn in 2006
- Global oral drug delivery market to be $37bn in 2006, and forecasts growth to $50bn by the end of 2010
5
Q
Reasons for Drug Delivery Systems Development
A
- Enhance efficacy and tolerance and increase compliance - PATIENT BENEFIT
- Key drivers of innovation
- Poor solubility
- Poor efficacy
- Frequent dosing regimens of current drugs
- Broaden a product line
- Extend patent life
- Revenues fall by ~70% when patent expires
- Delivery for biotherapeutics
6
Q
Drug Delivery Systems Development
A
- Modified -release strategies may be required for delivery of novel proteins, peptides, DNA, vaccines
- Only 40% of projects involving DDS are focused on novel compounds
7
Q
The Drug Development Process
A
8
Q
Drug Development of NCEs is Costly
A
- Average cost of developing NCE is now estimated to be as much as $800 million and are associated with high attrition rates
- Costs vary from around $500 million to $2,000 million depending on the therapy or the developing firm
-
Alternative drug delivery systems can be developed at less than 10% of this cost
- Much smaller risk of failure
9
Q
Formulation Development
A
- Lab scale= 5g
- Piolet= Kg’s
- Commercial= tons
10
Q
Limitations of Conventional Systems
1- Adverse Pharmacokinetics
A
- Many barriers between site of delivery and site of action
- Frequent dose; 1st pass metabolism; Harsh acidic condition;
- Fraction of dose reaching site may be small due to
- Poor absorption
- Metabolism
- Excretion
- Fraction of dose reaching site may be small due to
- Frequent dose; 1st pass metabolism; Harsh acidic condition;
- High First-pass metabolism
- Still usually inappropriate for controlled release by oral route
- May be avoided by alternative route - e.g. nasal, transdermal
- Still usually inappropriate for controlled release by oral route
11
Q
Limitations of Conventional Systems
2- Duration of Action
A
- Dosage Interval
- Short Half-life- frequent dosing is required
- Variable half-life
12
Q
Limitations of Conventional Systems
3- Therapeutic concentration
A
13
Q
Drug Plasma Level with Conventional Multiple Dosing vs. Modified Release
A
14
Q
Limitations of Conventional Systems
4- Drug burden
A
- Conventional system may require high drug levels
- MR can reduce the drug burden
- Less drug used in MR
- Deliver locally to site of action
- Largely retain drug at site
- Contraceptive Progesterone
- Delivered systemically 10 - 100 mg/d
- Progestasert IUD 10 - 100 µg/d
- Less drug used in MR
15
Q
E.g. of Commercial Drug Delivery Systems based Products
A
- Reduction in frequency of treatment
- Diclofenac – Voltarol Retard
- Improving bioavailability
- Ciclosporin – Neoral microemulsion
- Fast Action
- Diclofenac – Voltarol Rapid; Paracetamol - Actifast
- New delivery route
- GTN – transdermal; Insulin – inhalation
- Pain-free delivery
- Powderject, Bioject systems
- Taste-masking
- Paediatric Formulations
16
Q
Modified-release Systems
Rationale
1) dosage
2) Compliance
A
-
Dosage
- Controlled for fixed periods of time
- Rate and duration specified
- Reduced dosage compared to conventional systems
- Increased efficiency
-
Compliance
- Reduced dosage frequency
- Especially when asymptomatic, elderly
- Reduced dosage frequency
17
Q
Modified-release Systems
Rationale
3) Commercial 4) Variety
A
3) Commercial
- Savenges due to better disease management
- Adding value to generics
- Market expansion
- Creating new markets
- Novel therapies requiring specialised delivery
4) Variety
- Local delivery- Ocusert- pilocarpine
- Systemic delivery- glyceryl trinitrate
- Patient use- Nicotine patches
- Physician use
18
Q
Potential Limitations of modified systems
A
- General limitations
- Oral products are subject to physiological variation
- Limited duration (12 hour transit)
- Entrapment in tract
- Increase requirement for excipients
- If biodegradable, need to consider the toxicity of by-products
- Can be expensive
- Materials
- Fabrication process
- A surgical operation may be required for implants
- Difficulty in shutting off release if required
- Oral products are subject to physiological variation
19
Q
Potential Limitations of modified systems
A
- Although the overall burden may be decreased
- each unit may contain high drug levels
- Potential for leads leading to inadequate control of toxicity
- Construction on the suitability of drug candidates
- E.g. metabolic enhancement
- conventional bolus delivery can saturate the metabolic enzyme system
- Low, continuous levels of the drug may not saturate metabolic enzymes
- Therefore more extensive metabolism can occur and can result in reduced bioavailability
