Modified
1. Concept & Purpose
Modified-release (MR) dosage forms alter the timing, rate, or location of drug release to:
• Maintain therapeutic blood levels
• Reduce dose frequency
• Improve patient compliance
Types of Drug Release Profiles
Type Description
Immediate Release Rapid drug release after administration
Delayed Release Drug release after a time delay or in specific GIT condition
Extended Release Slow, prolonged drug release
Repeat Action Two or more doses at spaced intervals
Chronotherapy Release matches biological rhythm
2. Blood Level Comparison
Characteristic Immediate-Release Extended-Release
Plasma concentration Peaks & valleys More constant
Dosing frequency Multiple daily doses Once or twice daily
Compliance Lower Higher
Side effect risk Higher Reduced
3. Advantages of Modified-Release
Benefit Applies to
Less frequent dosing Repeat, Sustained
Reduced fluctuation in blood levels Sustained
Minimized side effects All types
Maintains drug levels during overnight gaps Sustained
Lower total drug use Sustained
Improved treatment for chronic diseases Sustained
4. Limitations of Modified-Release
• No quick withdrawal of drug if side effects appear
• Less flexibility in dose adjustment
• Unsuitable for drugs with:
o Very short or very long half-life
o Narrow therapeutic index
o Absorption limited to small GIT areas
• Risk of dose dumping
• Complex, costly manufacturing
:مالحظات
البخاخات أو الحبوب ممتدة المفعول مش مناسبة لحاالت الطوارئ •
أحيانًا صعب نتحكم بدقة في إطالق الدواء •
بسبب خصائصهاMR بعض األدوية ما بتصلح للـ •
5. Ideal Drug Candidate Properties
Property Preferred Value
Half-life 2–6 hours
Dose ≤ 325 mg
Absorption Throughout GIT
Therapeutic index Wide
Use Chronic treatment
6. Release Kinetics
Release Type Description
Zero-order Constant drug release rate
First-order Rate depends on remaining drug amount
Bimodal Two peaks; e.g. stomach then intestine
7. Formulation Strategies
A. Matrix (Monolithic) Systems
Type Release Mechanism
Lipid Matrix Solvent channels through wax matrix
Insoluble Polymer Drug diffuses through capillaries
Hydrophilic Colloid Gel layer forms & controls release
Components:
• Matrix formers: e.g. HPMC, alginates
• Channeling agents: NaCl, sugars
• Solubilizers: PEG, surfactants
• Gel modifiers: sugars, salts
B. Membrane-Controlled Systems
• Drug core coated with membrane
• Drug release by diffusion through membrane
Type Notes
Single-unit Coated tablet, may risk dose dumping
Multi-unit Pellets/beads in capsule, more consistent GI transit
Polymers used: Ethylcellulose, Eudragit, Polyvinyl acetate
C. Osmotic Pump Systems
Mechanism Drug core absorbs water → builds pressure → drug is pushed out via a
tiny hole
Key Characteristics:
• Zero-order release possible
• Release controlled by membrane properties & hole size
Advantages:
• Predictable release, unaffected by drug properties
Disadvantages:
• Expensive manufacturing (laser-drilled hole)
D. Ion-Exchange Resins
• Drug binds to resin via ionic interactions
• Release occurs when ions in GI tract exchange with drug
Applications:
• Controlled-release liquids (e.g. cough syrups)
8. Targeted Delivery Systems
Gastric Retentive Systems
Type Concept
Mucoadhesive Sticks to stomach lining
Floating Floats on gastric fluids
Swellable Expands in stomach to stay longer
Uses:
• Local action (e.g. H. pylori)
• Drugs with narrow absorption window
Colonic Delivery Systems
Targeting Mechanism Example
pH-sensitive coating Eudragit (dissolves at pH 7)
Time-dependent Relies on transit through small intestine
Bacteria-degradable Amylose, pectin (digested by colonic flora)
Uses:
• Treatment of IBD, colitis
• Systemic delivery of peptides
9. Delivery System Comparison Table
Feature Matrix Membrane- Osmotic Ion Exchange
Controlled Pump
Complexity Low– Medium–High High Medium
Medium
Zero-order Hard to Moderate Easy Possible
Release achieve
Risk of Dose Low Moderate–High Low Low
Dumping
Cost Low Medium High Low–Medium
Manufacturing Easy Requires coating Requires laser Requires resin
hole steps
Scalability Good More challenging Expensive Moderate
MR :أنواع
• Extended = إطالق بطيء
Delayed = إطالق مؤجل
•
• Repeat = إطالق مكرر
• Chrono = توقيت بيولوجي
:أنواع األنظمة
• Matrix
•Membrane
• Osmotic pump
• Ion exchange
:العوامل المهمة بالدواء
نص عمر مناسب •
قابلية امتصاص واسعة •
جرعة صغيرة •
هامش أمان واسع •