A Modified Release Drug Delivery System (MRDDS) is a type of drug delivery system designed to release a drug in a controlled manner to achieve better and longer-acting therapeutic outcomes.
Related Article: Targeted Drug Delivery System- Characteristics, Advantages, Disadvantages, Types, Applications
Elementary Osmotic Pump (EOP)
Push-Pull Osmotic Pump (PPOP)
Osmotic-controlled Release Oral Delivery System (OROS®)
Cancer Therapy: Doxorubicin-loaded nanoparticles
Vaccines: Microparticle-based vaccine delivery
Brain Drug Delivery: Nano-carriers crossing the blood-brain barrier
Antimicrobial Therapy: Antibiotic-loaded nanoparticles
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The hydrated gel controls drug diffusion and tablet erosion.
Mainly used in sustained-release matrix tablets.
Drug release occurs through slow diffusion via pores or cracks.
Common in non-erodible sustained release systems.
Used in injectables, microspheres, and implants.
Their main purpose is to prevent drug release in the acidic stomach and allow it to release in the more neutral/basic intestine (pH > 5.5).
Hydroxypropyl Methylcellulose Phthalate (HPMCP): Coating enteric granules, pellets
Methacrylic Acid Copolymers (Eudragit L, S): Colon targeting, delayed-release products
Polyvinyl Acetate Phthalate (PVAP): Coating for sensitive drugs
Shellac Natural resin: Traditional enteric coatings
Used in osmotic pump systems like OROS® tablets.
Unlike immediate-release formulations, MRDDS alters the timing, rate, or location of drug release to improve efficacy, reduce side effects, and enhance patient compliance.
Metformin Tablets Comparison
Example:
Types of Modified-Release Drug Delivery Systems
Let's understand different types of Modified Release Drug Delivery Systems (MRDDS).- Sustained Release (SR)
- Extended Release (ER/XR)
- Controlled Release (CR)
- Delayed Release (DR)
- Pulsatile Release
Sustained Release (SR)
Gradually releases the drug over time to maintain a consistent plasma concentration.
It's great because it reduces dosing frequency and helps to get long-term action.
It's great because it reduces dosing frequency and helps to get long-term action.
Example of Sustained Release Dosage Form:
Here you can see the difference between Metformin Tablets (Normal) and Metformin Sustained Release Tablets (SR). This comparison helps you to easily understand the basics about the Normal/Immediate release system and the Sustained or Prolonged Release Dosage Form.
| Feature | Metformin Tablets (Normal) | Metformin Sustained Release Tablets (SR) |
|---|---|---|
| Release Pattern | Immediate release into the body | Slow, controlled release over time |
| Dosing Frequency | 2–3 times per day (with meals) | 1–2 times per day |
| Peak Blood Level | Rapid rise after taking | Gradual rise, steady levels |
| Stomach Side Effects | Higher (nausea, diarrhea common) | Lower (gentler on stomach) |
| Convenience | Less convenient (multiple doses) | More convenient (once or twice daily) |
| Brand Examples | Glyciphage, Glucophage | Glyciphage SR, Glucophage XR |
| Purpose | Controls blood sugar but can spike drug levels | Controls blood sugar with stable drug levels |
Extended Release (ER/XR)
One that allows a reduction in dosing frequency compared to that presented by a conventional dosage form. It is designed to release medication in a controlled manner at a pre-determined rate, duration, and location in the body to achieve and maintain optimum therapeutic blood levels of the drug.
Repeat-action tablets are one type of extended-release dosage form.
Examples:
- Seloken XL 25 Tablet [Metoprolol Succinate Extended Release 25mg Tablet]
- Faronem ER 300mg Tablet [Faropenem Extended Release 300mg Tablet]
Controlled Release (CR)
Provides a predictable and constant drug release over a specific period.
Ensures steady therapeutic levels, minimizing fluctuations.
Ensures steady therapeutic levels, minimizing fluctuations.
- Epimaz 200mg Tablet CR [Carbamazepine Controlled Release 200mg Tablet]
- Unicontin-E 400 Tablet CR [Theophylline Controlled Release 400mg Tablet]
Delayed Release (DR)
The drug is released at a specific time or location in the body (e.g., enteric-coated tablets that dissolve in the intestine). These are dosage forms designed to release the drug at a time other than promptly after administration. The delay may be time-based or based on the influence of environmental conditions such as GI, pH, enzyme, pressure, etc.Examples: Enteric-coated dosage forms like enteric-coated aspirin, other NSAIDs, etc
Targeted Release
Directs the drug to a specific site in the body.Examples: Nanoparticles for cancer therapy.
Pulsatile Release
Mimics the body's natural rhythms by releasing the drug in pulses (e.g., for conditions like asthma or arthritis).Advantages of Modified-Release Drug Delivery Systems
- Enhances therapeutic efficacy.
- Reduces dosing frequency and improves patient compliance.
- Minimizes side effects by avoiding peak plasma drug levels.
- Reduces drug wastage and improves cost-effectiveness.
Pharmaceutical Technologies used behind Modified Release Drug Delivery Systems
| Technologies | Description | Examples |
|---|---|---|
| Matrix Systems | Drug is embedded in a polymer matrix. Drug slowly diffuses out over time. | Metformin SR uses hydrophilic matrix (HPMC) |
| Reservoir Systems | Drug is surrounded by a rate-controlling membrane. Drug is released at a controlled rate through the membrane. | Coated beads, capsules |
| Osmotic Systems | Water enters a tablet, creating pressure that pushes drug out at a steady rate. | OROS® systems (e.g., Concerta) |
| Hydrophilic Gels | Tablet swells into a gel after swallowing, slowing down drug release. | Many sustained-release tablets |
| Ion Exchange Resins | Drug binds to a resin, and the drug is slowly released by exchanging ions (like Na⁺ or K⁺) in the body. | Cationic resin-based tablets |
| Multi-particulate Systems | Tiny coated granules inside capsules; each granule releases drug at different times. | Sprinkle capsules, ER beads |
| Floating Systems | Tablets float on stomach fluids and release drug slowly while floating. | Gastric-retentive systems |
| Mucoadhesive Systems | Tablets stick to mucosal surfaces (e.g., in stomach/intestine) to release drug locally. | Buccal/sublingual MR tablets |
- Matrix Systems (hydrophilic/hydrophobic polymers control drug diffusion)
- Reservoir Systems (drug core surrounded by rate-controlling membranes).
The drug is surrounded by a rate-controlling membrane.
- Osmotic Systems (release drug via osmotic pressure).
Elementary Osmotic Pump (EOP)
Push-Pull Osmotic Pump (PPOP)
Osmotic-controlled Release Oral Delivery System (OROS®)
- Microparticles/Nanoparticles (enhanced targeting and prolonged release).
Cancer Therapy: Doxorubicin-loaded nanoparticles
Vaccines: Microparticle-based vaccine delivery
Brain Drug Delivery: Nano-carriers crossing the blood-brain barrier
Antimicrobial Therapy: Antibiotic-loaded nanoparticles
Related Article: Nanoparticles- Characterization, Preparation Methods, Applications
Types of Polymers and Materials Used in Modified Release Drug Delivery Systems (MRDDS)
Hydrophilic Matrix Formers
Polymers like Hydroxypropyl Methylcellulose (HPMC), Sodium Carboxymethylcellulose (NaCMC), and Xanthan Gum are used to form a gel layer upon hydration.The hydrated gel controls drug diffusion and tablet erosion.
Mainly used in sustained-release matrix tablets.
Hydrophobic Matrix Formers
Materials such as Ethylcellulose, Polyvinyl Acetate (PVAc), and Hydrogenated Castor Oil are employed to create a water-insoluble matrix.Drug release occurs through slow diffusion via pores or cracks.
Common in non-erodible sustained release systems.
Biodegradable Polymers
These polymers control drug release through polymer degradation and erosion.Used in injectables, microspheres, and implants.
Examples of Biodegradable Polymers:
Polylactic Acid (PLA), Polyglycolic Acid (PGA), and Poly(lactic-co-glycolic acid) (PLGA) degrade by hydrolysis of their ester bonds.
Enteric Coating Polymers
Enteric coatings are special polymer coatings applied to oral drug formulations.Their main purpose is to prevent drug release in the acidic stomach and allow it to release in the more neutral/basic intestine (pH > 5.5).
Examples of Enteric coatings:
Cellulose Acetate Phthalate (CAP): Coating tablets, capsulesHydroxypropyl Methylcellulose Phthalate (HPMCP): Coating enteric granules, pellets
Methacrylic Acid Copolymers (Eudragit L, S): Colon targeting, delayed-release products
Polyvinyl Acetate Phthalate (PVAP): Coating for sensitive drugs
Shellac Natural resin: Traditional enteric coatings
Osmotic Agents
Water influx builds pressure, forcing the drug solution out through a laser-drilled hole.Used in osmotic pump systems like OROS® tablets.
Examples of Osmotic Agents: Sodium Chloride, Mannitol, etc.
Film-Coating Polymers
They form a semi-permeable coating around the tablet or pellet. Drug release is controlled by diffusion through the polymer membrane.Examples of film coating polymers: Methacrylic Acid Copolymers (Eudragit RS/RL), Ethylcellulose, etc.
Mucoadhesive Polymers
Polymers have a high affinity for mucosal tissues. That helps prolong residence time.
Applied in buccal, nasal, vaginal, and gastrointestinal mucoadhesive systems.Examples of Mucoadhesive Polymers: Chitosan, Polycarbophil, Carbopol, etc.
| Material Type | Purpose/Use | Examples |
|---|---|---|
| Plasticizers | Improve flexibility of polymer coatings | Glycerol, Triethyl citrate |
| Osmotic Agents | Create osmotic pressure in osmotic pumps | Sodium chloride, Mannitol |
| Pore Formers | Control porosity in coating membranes | PEG, PVP (Polyvinylpyrrolidone) |
| Surfactants | Enhance wetting and drug solubilization | Tween 80, Span 20 |
| Stabilizers | Protect drug and polymers from degradation | Antioxidants (BHT, BHA) |
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