What is a Controlled Drug Delivery System?

 It's a system designed to release drugs slowly and consistently over an

extended period.
 Typically, it uses a hydrophilic polymer matrix to achieve controlled drug
release.
 The goal is to release the right amount of the drug at specific intervals and at
the intended location in the body to maintain therapeutic drug levels in the
blood.

Advantages of Oral Controlled Drug Delivery:

 Offers controlled release rates and maintains a consistent dose in the

bloodstream.
 Achieved by using swelling polymers, waxes, or a combination to control the
drug release rate.
 A reservoir system can also help control the release rate.

Goals of Controlled Release Drug Delivery:

 Reduce the frequency of drug dosing.

 Lower the required drug dosage.
 Deliver the drug evenly and predictably.
 The system releases drugs steadily at a predetermined rate over a set time,
either throughout the body or directly to the target organ.
 Benefits include better control of drug levels in the blood, reduced need for
frequent dosing, fewer side effects, increased effectiveness, and a constant
drug delivery.
A polymer is a large molecule composed of repeating units called monomers, which are
chemically bonded together to form a long-chain or networked structure. Polymers can be
natural or synthetic and are characterized by their high molecular weight

Advantages of Polymer-Based Drug Delivery Systems:

1. Controlled Release: Polymers release drugs slowly, ensuring a steady

therapeutic effect with less frequent dosing.
2. Improved Bioavailability: Some polymers enhance the absorption of poorly
soluble drugs, making them more effective.
3. Targeted Delivery: Polymers can deliver drugs directly to specific tissues,
reducing side effects and increasing drug concentration where needed.
4. Prolonged Action: Polymer formulations extend drug effects, reducing how
often patients need to take medication.
5. Protection of Sensitive Drugs: Polymers shield drugs from environmental
factors, preserving their potency.
6. Reduced Toxicity: Polymer systems minimize harm to healthy tissues,
reducing side effects.
7. Customization: Polymers can be tailored to match a drug's properties and
release needs.
8. Reduced Dosing: Long-acting polymers cut down the number of doses,
making treatment more convenient and improving compliance.

Disadvantages of Polymer-Based Drug Delivery Systems:

1. Complex Formulation: Creating these systems is intricate and time-

consuming, demanding deep knowledge of polymer chemistry and drug
interactions.
2. Burst Release: Some polymer systems release too much drug at the start,
potentially leading to ineffective treatment or side effects.
3. Biocompatibility Concerns: The choice of polymer and its breakdown
products can cause biocompatibility issues, possibly resulting in adverse
reactions or tissue inflammation.
4. Size and Shape Constraints: Polymer carriers may have limitations in size and
shape, restricting their use for specific administration methods or drug
delivery needs.
5. Limited Drug Compatibility: Not all drugs work well with polymer delivery
systems; some may need modifications to be effective.
6. Degradation Rate Variability: Polymer degradation rates can vary due to
factors like pH, temperature, and enzymatic activity, affecting drug release
consistency.
 7. Regulatory Challenges: Getting regulatory approval for new polymer-based
drug delivery systems is challenging due to their complexity and the
requirement for comprehensive safety and efficacy data.
8. Cost: Developing and producing polymer-based systems is often more
expensive than conventional formulations, potentially impacting affordability
and access to treatment.

Aspect Sustained Release Controlled Release

Gradual and continuous release of a

drug over an extended period, Deliberate and precise control of the drug
maintaining constant therapeutic release rate, which may follow specific
Definition concentrations. predetermined patterns.

Can vary according to a programmed

release profile, which may include various
Release Profile Generally constant release rate. patterns (e.g., constant, exponential).

Transdermal patches, osmotic pumps,

Examples Extended-release tablets, capsules. microsphere-based drug delivery systems.

Can vary according to a programmed

release profile, which may include various
Release Profile Generally constant release rate. patterns (e.g., constant, exponential).

Can be customized to release at different

Rate of Release Relatively consistent. rates during the course of treatment.

Purpose Reduce dosing frequency, enhance Achieve specific therapeutic goals by

patient compliance, and maintain optimizing drug delivery, targeting sites of
 Aspect Sustained Release Controlled Release

steady drug efficacy. action, and minimizing side effects.

Less flexibility in altering release High flexibility in tailoring release profiles

Flexibility profiles. for different drugs and therapeutic needs.

Common in chronic conditions where Used for conditions requiring precise control
maintaining stable drug levels is of drug release, such as chronotherapy or
Applications crucial. targeting specific tissues.

Beneficial for drugs with complex

Clinical Useful for drugs with a narrow pharmacokinetics or those requiring
Considerations therapeutic window. synchronization with circadian rhythms.

Aspect Sustained Release Controlled Release

Typically maintains a relatively Release rates may be modulated to achieve

Release Rate constant release rate throughout the specific therapeutic goals, which can include
Stability dosage form's duration. variations in release rate over time.

Enhances patient adherence by

reducing the frequency of dosing, May require complex dosing schedules but
Patient Adherence making it more convenient. can provide tailored therapy.

Drug Delivery Often relies on diffusion or erosion of Utilizes various mechanisms, including
Mechanisms the drug-containing matrix to control diffusion, osmosis, and matrix erosion, as
 Aspect Sustained Release Controlled Release

well as specialized technologies like

release. microencapsulation.

Can vary widely; some controlled release

Typically administered less frequently systems require less frequent dosing, while
Dosing Frequency (e.g., once daily or less often). others may still require daily dosing.

Reduces the occurrence of high peak

concentrations and low trough Can be designed to minimize peaks and
Peak and Trough concentrations compared to troughs, but the degree of control varies
Concentrations immediate-release formulations. based on the release profile chosen.

Often used in chronic conditions where Valuable in conditions requiring precise

steady drug levels are important (e.g., drug delivery timing (e.g., sleep disorders,
Clinical Indications hypertension, diabetes). hormone replacement therapy).

Development may involve more extensive

Development Generally less complex to develop due formulation and testing to achieve the
Complexity to the consistent release profile. desired release pattern.

Regulatory approval may be

straightforward for sustained release May require more rigorous testing and
Regulatory products due to their well-defined documentation to gain regulatory approval,
Considerations release profiles. especially for complex release profiles.

Polymers of Natural Origin:

 1. Chitosan: Chitosan, derived from chitin found in the exoskeletons of
crustaceans, is used in drug delivery to improve drug solubility, prolong drug
release, and enhance bioavailability. It is commonly used in oral drug delivery
systems and mucoadhesive drug formulations for mucosal drug delivery.
2. Alginate: Alginate, extracted from brown algae, is used in the formulation of
drug-loaded microspheres and hydrogels. It is particularly suitable for
controlled release in the gastrointestinal tract and for applications like wound
dressings.
3. Gelatin: Derived from collagen, gelatin is used to create biodegradable drug
delivery matrices and microcapsules. It finds applications in controlled release
formulations and tissue engineering scaffolds.
4. Pectin: Pectin, a naturally occurring polysaccharide in plant cell walls, is used
in the development of mucoadhesive drug delivery systems, particularly for
oral and nasal drug administration.
5. Hyaluronic Acid: Hyaluronic acid, a component of the extracellular matrix, is
employed in drug delivery systems for targeting tissues and cells. It is
commonly used in ophthalmic drug delivery and for skin rejuvenation.

Polymers of Semisynthetic Origin:

1. Cellulose Derivatives: Semisynthetic derivatives of cellulose, such as

hydroxypropyl cellulose (HPC) and methylcellulose (MC), are used in various
drug delivery systems. They contribute to controlled release in oral tablets and
capsules.
2. Poly(lactic-co-glycolic acid) (PLGA): PLGA is a biodegradable polymer
commonly used in the development of microspheres, nanoparticles, and
implantable drug delivery systems. It enables sustained drug release and is
widely used in pharmaceuticals.
3. Eudragit Polymers: Eudragit polymers are acrylic-based copolymers with pH-
dependent solubility properties. They are used in enteric coatings for oral
drug delivery, ensuring drug release in the desired region of the
gastrointestinal tract.
4. Polycaprolactone (PCL): PCL is used in the development of biodegradable
implants and microparticles for controlled drug release. It is especially suitable
for long-acting drug delivery applications.
5. Hydroxypropyl Methylcellulose Acetate Succinate (HPMCAS): HPMCAS is
a semisynthetic polymer used as a carrier in solid dispersion formulations to
improve drug solubility and dissolution rates, enhancing oral bioavailability.
6. Polysorbates (Tween): Polysorbates are used as surfactants and emulsifiers in
parenteral drug formulations. They help improve the solubility and stability of
poorly water-soluble drugs.
7. Polyethylene Glycol (PEG): PEG is used in the development of pegylated
drug formulations, enhancing drug stability and extending circulation time in
the body, particularly in biopharmaceuticals and protein therapeutics.
1.1.8. Properties Relevant to Controlled Drug Release

Controlled drug delivery systems rely on several crucial factors that can be
categorized into two major groups: physicochemical properties and biological
properties. Let's explore these properties in more depth:

1.1.8.1. Physicochemical Properties

1. Molecular Size and Diffusivity:
 Diffusivity is essential for drugs in sustained release forms, as they need
to pass through biological membranes and rate-controlling
membranes.
 Diffusivity depends on the molecular size or weight of the drug.
 The diffusion coefficient values for drugs with intermediate molecular
weights (150-400) through flexible polymers typically range from 10 to
10 cm³/sec.
 Drugs with molecular weights >500 have very low diffusion coefficients,
making their quantification challenging.
 High molecular weight drugs exhibit slow release kinetics in sustained
release devices where diffusion through a polymeric membrane or
matrix controls release.
2. Aqueous Solubility:
 Drugs are often weak acids or weak bases.
 Formulating sustained release dosage forms is difficult for drugs with
low water solubility.
 Highly water-soluble drugs dissolve quickly, leading to rapid absorption
and higher blood concentrations.
 Delaying the release of highly water-soluble drugs can be challenging,
especially with high drug doses.
 pH-dependent solubility in the gastrointestinal tract (GIT) can further
complicate sustained release formulations due to pH variations.
3. pH and pKa:
 Highly ionized drugs are not suitable for oral sustained release
formulations.
 Unionized drugs are absorbed effectively, while ionized drugs have
much lower permeation rates (3-4 times less).
 Acidic drugs with pH-sensitive ionization have pKa values around 3.0-
7.5, while basic drugs have pKa values around 7.0-11.0.
 Ideal drugs for positive absorption should be primarily unionized (0.1-
5.0%) at the absorption site.
4. Partition Coefficient:
 The partition coefficient (K) indicates the fraction of a drug in an oil
phase compared to an adjacent aqueous phase.
 K influences drug permeation across biological membranes and
diffusion through rate-controlling membranes or matrices.
 High K values suggest high oil solubility and better partitioning into
membranes.
 Apparent oil or water partition coefficient is a major evaluation criterion
for a drug's membrane permeability.
5. Permeability:
  Permeability for passive transport across intestinal epithelium is
influenced by Log P (lipophilicity), molecular size, and drug polarity.
 Polarity is assessed based on the number of H-bond acceptors and
donors on the drug molecule.
6. Mechanism and Site of Absorption:
 Drugs absorbed via carrier-mediated transport are not suitable for
controlled release systems.
 For example, water-soluble vitamins like vitamin B12 require carrier
proteins for absorption, making them unsuitable for sustained release.
7. Drug Stability:
 Stability is crucial for oral dosage forms, as drug loss due to acid
hydrolysis or metabolism in the GIT can occur.
 Solid drugs degrade more slowly than those in suspension or solution,
improving bioavailability for unstable drugs.
 Controlled drug delivery systems protect drugs from enzymatic
degradation, making them beneficial for highly unstable drugs.
8. 1.1.8.2. Biological Properties Relevant to Controlled and Sustained-
Release Dosage Forms
9. In the selection of drug candidates for controlled and sustained-release
dosage forms, various biological properties of the drugs play a crucial role.
These properties impact how the drugs are absorbed, distributed,
metabolized, and eliminated, as well as their overall therapeutic effectiveness.
Here, we delve into the intricate details of these biological properties:
10. 1) Absorption: The rate, extent, and uniformity of drug absorption are pivotal
factors when formulating drugs into sustained release dosage forms. In such
formulations, it's essential that the rate of drug absorption is rapid compared
to its release, as drug release, rather than absorption, becomes the rate-
limiting step. This is particularly critical in oral administration. For example, if a
drug's transit time through the absorption half-life is 4 hours, it necessitates a
minimum absorption rate constant (Ka) of 0.17-0.23 hours to achieve 80-95%
absorption over a transit time of 9-12 hours. Drugs with rapid absorption (Ka
>> 0.23-1 hour) and first-order release rates (Kr < 0.17-1 hour) result in poor
bioavailability in many patients. Hence, drugs that are slowly absorbed face
challenges when formulating controlled release dosage forms, as they must
meet the Kr <<< Ka criteria.
11. 2) Distribution: Drug distribution in tissues and cells is another critical factor
that can lower drug concentration in circulation, affecting drug elimination
kinetics. This distribution process often involves the binding of drugs to
tissues and blood proteins. When drug molecules are bound to proteins, they
become inactive and cannot easily permeate biological membranes.
Additionally, a high degree of protein binding can lead to prolonged
therapeutic action. An important parameter in drug distribution is the
apparent volume of distribution, which reflects the magnitude of distribution
 and protein binding within the body. It's defined as the proportionality
constant of plasma drug concentration to the total amount of drug in the
body. Prior to designing sustained release systems, it's imperative to gather
information about the drug's disposition in the body.
12. 3) Protein Binding: Many drugs have an affinity for binding to plasma
proteins, which can significantly influence the duration of their therapeutic
effects. When drugs bind to blood proteins, they are often recirculated in the
bloodstream rather than being eliminated from the body. This binding serves
as a reservoir for a prolonged release of the drug. Moreover, the rate and
extent of oral drug absorption can be affected by interactions with proteins, as
well as the duration of binding with mucin-like proteins.
13. 4) Metabolism: Drug metabolism involves either the inactivation of active
drugs or the conversion of inactive drugs into active metabolites. This process
occurs in various tissues, some of which contain higher levels of enzymes
responsible for drug metabolism. Drugs that undergo metabolism before
absorption, whether in the lumen of the gastrointestinal tract or in intestinal
tissues, are released at a slower rate. As a result, they often exhibit reduced
bioavailability. Enzyme systems in the intestinal wall are typically saturable.
When drugs are released slowly to these regions, less total drug is presented
to the enzymatic process during a specific period, leading to complete
conversion into metabolites. One viable solution for drugs susceptible to
enzymatic metabolism is to formulate them as prodrugs. However, drugs that
can induce or inhibit enzyme synthesis are considered poor candidates for
sustained release delivery systems, as they struggle to maintain uniform blood
levels. Additionally, drugs whose bioavailability varies due to hepatic first-pass
metabolism or intestinal metabolism are not ideal candidates for sustained
release delivery systems.
14. 5) Elimination or Biological Half-Life: An oral sustained release product
aims to maintain therapeutic blood levels over an extended time period. To
achieve this, the rate at which the drug enters the bloodstream should be
similar to its rate of elimination, quantitatively described by the half-life of the
drug. Each drug has its unique elimination rate, which encompasses all
processes involved in elimination, such as metabolism, urinary excretion, and
other processes responsible for removing the drug from blood circulation. The
best candidates for sustained release delivery systems are drugs with short
half-lives, as this reduces the dosing frequency. However, drugs with
extremely short biological half-lives require large amounts of the drug in each
dosage unit to maintain the sustained effect, potentially making the dosage
form impractical. In essence, drugs with a half-life of less than 2 hours are
considered unsuitable for sustained release delivery systems, while those with
a long half-life exceeding 8 hours are also deemed inappropriate, as their
effects are already sustained.
15. 6) Duration of Action: The duration of a drug's action is a significant
consideration in the formulation of controlled release delivery systems. Factors
like drug distribution, metabolism, and elimination affect the overall duration
of drug action. The half-life of a drug essentially represents its residence time
in the body. Drugs with longer elimination half-lives (greater than 8 hours) are
inherently sustained in the body, and therefore, they are not typically
formulated as controlled release dosage forms. Conversely, drugs with shorter
half-lives (less than 2 hours) are also excluded from controlled release
formulations, as these would require large drug doses or result in impractical
dosing regimens.
16. 7) First-Pass Metabolism: First-pass metabolism refers to the enzymatic
degradation or alteration of an orally administered drug after its absorption,
before it enters the systemic circulation. While the liver is the primary site of
first-pass metabolism, other potential sites include the gastrointestinal tract,
blood, vascular endothelium, lungs, and the site from which venous samples
are taken. Examples of drugs that undergo extensive first-pass metabolism
include amitriptyline, 5-fluorouracil, hydralazine, isoprenaline, lignocaine,
lorcainide, pethidine, metoprolol, morphine, neostigmine, nifedipine,
pentazocine, and propranolol. Drugs subject to extensive hepatic first-pass
metabolism when administered in controlled release forms may not reach the
desired concentrations in the body. Drugs with variable bioavailability due to
first-pass metabolism are also challenging to formulate as controlled release
systems, as the problem of drug loss becomes dose-dependent, reducing
overall bioavailability when the drug is released slowly over an extended
period. Extensive first-pass metabolism can adversely affect the blood
concentration required for the desired therapeutic effect.
17. 8) Size of the Dose: When orally administering drugs, there is an upper limit
to the bulk size of each dose. A single dose of 0.5-1.0 gram is generally
considered the maximum for both conventional and sustained release dosage
forms. Drugs requiring larger doses can be administered in multiple smaller
amounts or formulated as liquid systems. It is also essential to consider the
safety margin when administering large doses of a drug, especially when the
therapeutic range is narrow.
18. 9) Dosing Frequency: The dosing frequency refers to how often a drug dose
is administered within a specific time period. Well-designed controlled release
delivery systems typically reduce dosing frequency while maintaining steady
drug concentrations in the blood and target tissue cells. For instance, the use
of nanoformulations for drugs like natamycin suspension (5%) has led to a
reduction in dosing frequency. Initially, patients may have had to take one or
two drops hourly, but with nanoformulation, the dosing frequency was
extended to one drop every 5 hours. This not only decreased the overall dose
but also prolonged the
uses of air suspension techniques in novel drug delivery systems presented in a
point-wise format:

1. Uniform Particle Size Distribution:

 Creation of consistent drug particle sizes for uniform dosing.
2. Inhalable Drug Formulations:
 Production of dry powder formulations for respiratory drug delivery.
 Effective for conditions like asthma and COPD.
3. Controlled Release:
 Formulation of controlled-release drug products.
 Encapsulation in microparticles or nanoparticles for prolonged
therapeutic effects.
4. Taste Masking:
 Development of palatable drug formulations, especially for pediatric
patients.
 Coating or encapsulation to mask bitter tastes.
5. Improved Bioavailability:
 Enhancement of drug solubility, particularly for poorly water-soluble
drugs.
 Formulation into nanoparticles or solid lipid nanoparticles.
6. Targeted Drug Delivery:
 Application in specialized drug delivery systems for precise targeting.
 Minimization of systemic side effects and enhanced drug efficacy.
7. Vaccine Formulation:
 Creation of stable dry powder vaccines for easy storage and
distribution.
 Crucial for global health initiatives and remote areas.
8. Combination Therapies:
 Formulation of combination drug products in a single dosage form.
 Improved patient compliance and simplified administration.
9. Personalized Medicine:
 Customization of drug formulations to match individual patient needs.
 Tailoring of drug release profiles and dosages.
10. Biological Drug Delivery:
 Adaptation for the delivery of biologic drugs, such as monoclonal
antibodies and peptides.
 Maintaining stability and activity of biologics.
11. Enhanced Drug Stability:
 Creation of stable drug formulations less susceptible to degradation.
12. Dissolution Rate Enhancement:
 Improving the dissolution rate of poorly soluble drugs for faster onset
of action.
13. Long-Acting Injectable Formulations:
 Formulation of long-acting injectable drugs with sustained release
properties.

1. Transmucosal Permeability Overview

 Drug permeation across epithelial membranes involves two routes:
transcellular and paracellular.
 Epithelial membranes, like skin and gastrointestinal mucosa, are often
considered lipoidal barriers, but they have additional complexities.
 Transmembrane permeation involves both a lipoidal pathway and an
aqueous pore pathway.
2. Nasal Mucosal Membrane
 The absorption of β-adrenoreceptor-blocking drugs in humans
correlates with drug lipophilicity, suggesting the presence of a lipoidal
pathway.
 However, lipophilicity alone does not determine nasal absorption rates.
 Nasal mucosa is considered a modified lipoidal barrier for lipophilic
drugs.
 For hydrophilic drugs, the presence of aqueous pore channels in the
nasal mucosa is indicated.
3. Transmucosal Permeation of Polar Molecules
 Polar molecules, such as peptide-based pharmaceuticals, primarily
permeate via the paracellular route.
 Barriers to paracellular permeation include:
 The basal lamina barrier, influenced by molecule size and
reactivity.
 Membrane-coating granules that impede the penetration of
water-soluble peptides or proteins.
 The variable barrier function of the keratin layer in oral mucosa.
 Similar mechanisms and rates of transmucosal permeation
across different regions of oral mucosa.
4. Rectal Mucosa
 Drug absorption through rectal mucosa aligns with the pH-partition
theory.
 Ionic and lipid-insoluble drugs are poorly absorbed, while lipid-soluble
drugs are rapidly absorbed.
 Rectal mucosa is considered a simple lipoidal barrier.
 The presence of aqueous pore channels is limited in rectal mucosa
compared to other gastrointestinal regions.
5. Vaginal Mucosal Membrane
 The vaginal mucosa, similar to the nasal mucosa, comprises a lipoidal
pathway and an aqueous pore pathway.
  Permeability coefficients of aliphatic alcohols increase with lipophilicity,
highlighting the importance of the lipoidal pathway.
 Aqueous diffusion layer on the vaginal mucosal surface is
approximately 310μm thick.
 Studies on alkanoic acids suggest the importance of the aqueous pore
pathway, especially for shorter alkyl chain compounds.
 Vaginal mucosa contains semi-polar regions, not purely lipophilic or
hydrophilic.
 Intercellular lipids restrict the absorption of large, water-soluble
compounds in some cases.
 Absorption of hydrophilic compounds varies with the estrous cycle
stages, with increased absorption during proestrus and diestrus due to
loosening of epithelial cell junctions in cycling animals.

MDDS.
These are the systems in which formulation interact with mucosal layer and increase the
residential time of formulation at the site of administration for better absorption  These
systems are designed to provide Controlled/Sustained Release of drug at the site of
administration
IDDS.
CONEPT OF IMPLANT
The concept of implants in the medical field is a crucial one, as it involves the use of
man-made devices to replace missing or damaged biological structures or enhance
the functioning of existing ones. Implants play a significant role in modern medicine
and can be categorized into non-degradable and biodegradable systems.

Non-Degradable Systems: Non-degradable implantable drug delivery systems are

designed to release medications or substances into the body over an extended
period. There are several types of non-degradable systems:

1. Polymeric Matrix Systems: In these systems, the drug is uniformly

distributed within a solid, non-biodegradable polymer matrix. The drug is
released through slow diffusion from the matrix, providing sustained drug
release.
2. Reservoir Systems: Reservoir-type systems consist of a compact drug core
enclosed by a permeable non-degradable membrane. The thickness and
permeability of the membrane control the diffusion of the drug into the body.
This system can achieve zero-order release kinetics but requires minor surgery
for removal after drug release. Membrane rupture can lead to drug dumping
and potential toxic side effects.
3. Magnetically Controlled Release Systems: These systems incorporate small
magnetic beads within a polymer. When exposed to an external oscillating
magnetic field, they release larger quantities of the drug quickly. This type of
system allows for precise control of drug release through magnetic
stimulation.

Biodegradable Systems: Biodegradable implantable drug delivery systems are more

popular than non-degradable ones due to several advantages:
 1. Inert Polymer Use: Biodegradable systems are made from inert polymers that
are absorbed or excreted by the body, eliminating the need for surgical
removal.
2. Patient Acceptance: The biodegradable nature of these systems enhances
patient acceptance and compliance as they dissolve naturally after treatment.

However, developing biodegradable systems is more complex, as various factors

must be considered:

 Degradation Kinetics: The polymer's degradation kinetics should remain

constant to ensure sustained drug release.
 Factors Affecting Degradation: Factors like body pH, temperature changes,
and surface area can affect the degradation rate of the system.
 Surface Area Consideration: Changes in the shape of the drug delivery
system during erosion can impact drug release. Shapes with a constant
surface area, such as flattened slabs, can achieve a zero-order release kinetic
profile.
 Drug Diffusion Rate: Drug diffusion from the polymer matrix should match
the bioerosion rate of the system, especially for drugs with narrow therapeutic
indices.

There are two main types of biodegradable delivery systems:

1. Reservoir Systems: Similar in structure to non-degradable reservoir systems,

these biodegradable systems consist of an exterior polymeric membrane that
degrades more slowly than the expected rate of drug diffusion through the
membrane. This ensures complete drug release, with the membrane
degrading and eventually being excreted in vivo.
2. Monolithic Systems: In monolithic systems, the drug is dispersed within a
polymer matrix, which slowly erodes in vivo due to biological processes at a
controlled rate.

Common biodegradable polymers used in these systems include polyglycolic acid,

polylactic acid, polyglycolic-lactic acid, polyaspartic acid, and polycaprolactone. Some
systems may also utilize ethyl vinyl acetate copolymers for the delivery of
macromolecular drugs, such as insulin.

CONEPT OF OSMOTIC PUMP

Introduction:

 Osmotic pump controlled release preparations are effective dosage forms that
are independent of physiological and physiochemical factors.
  They optimize various formulation parameters to control the rate and pattern
of drug release.
 These systems can deliver drugs with varying solubility, including insoluble
drugs as sub-saturated solutions.
 Osmotic pumps can be used for high drug doses and are compatible with
drugs of varying solubility.

Advantages:

1. Zero-order delivery rate.

2. Delayed or pulsed drug delivery.
3. Greater delivery rate compared to diffusion-based systems.
4. Predictable in vitro and in vivo drug delivery rates.
5. Independent of pH variations and agitation in the environment.
6. Highly predictable and programmable drug release.
7. Drug delivery occurs in a solution form ready for absorption.
8. Independent of delivery orifice size within limits.
9. Compatible with drugs of varying solubility.
10. Easily fabricated using conventional pharmaceutical manufacturing
equipment.

Disadvantages:

1. Requires special equipment for making the orifice, making it expensive.

2. Size of the pores in the system is critical.
3. Dose dumping may occur due to film defects.
4. Retrieval therapy is not possible in case of unexpected adverse events.
5. Residence time in the body varies with gastric motility and food intake.
6. May cause irritation or ulcers due to the release of saturated drug solution.

Principle of Osmosis:

 Osmosis is the process where solvent (usually water) moves from an area of
lower solute concentration to an area of higher solute concentration across a
semi-permeable membrane.
 Osmotic pressure is directly proportional to solute concentration and absolute
temperature.

Basic Components of Osmotic Pumps:

1. Drug: Water-soluble or water-insoluble drugs with short biological half-lives,

high potency, and suitability for chronic treatment.
2. Osmotic Agents: Ionic compounds (inorganic salts or hydrophilic polymers)
that generate osmotic pressure, maintaining a concentration gradient across
the membrane.
3. Semi-Permeable Membrane: Selectively permeable membrane for controlled
drug release.
4. Plasticisers: Used in the coating membrane to control polymer permeability.
5. Flux Regulators: Added to regulate fluid permeability.
6. Wicking Agents: Draw water into the system, creating channels for increased
surface area.
7. Pore-Forming Agents: Used in poorly water-soluble drugs and controlled
porosity systems.
8. Coating Solvents: Used to make polymeric solutions for the device wall.
ALZET osmotic pumps and how they operate:

1. Purpose and Use:

 ALZET osmotic pumps are small, implantable devices used for research
purposes in laboratory animals such as mice and rats.
 They are designed to continuously deliver drugs, hormones, or other test
agents at controlled rates for a specified duration, ranging from one day to six
weeks.
 These pumps eliminate the need for external connections or frequent
handling, making it possible to avoid repeated dosing during nights or
weekends.

2. Implantation Location:

 ALZET pumps are typically implanted either subcutaneously (under the skin) or
intraperitoneally (within the abdominal cavity) of the animal, depending on
the desired route of administration.

3. Systemic and Localized Delivery:

  They can be used for systemic administration, allowing the controlled release
of substances throughout the entire circulatory system.
 ALZET pumps can also be attached to a catheter to enable localized drug
delivery, which is useful for targeting specific tissues or organs.
 Different administration routes, such as intravenous, intracerebral, or intra-
arterial infusion, can be achieved using ALZET pumps, making them versatile
for various research applications.

4. Osmotic Displacement Operation:

 ALZET pumps operate based on the principle of osmotic displacement.

 The core of the pump contains an empty reservoir, which is intended to be
filled with the drug or hormone solution that needs to be delivered.
 This reservoir is separated from the surrounding chamber containing a high
concentration of salt by a semi-permeable membrane.

5. Water Influx and Drug Delivery:

 The chamber surrounding the reservoir contains a high concentration of salt.

 Due to this high salt concentration, water from the surrounding tissues enters
the pump through the semi-permeable membrane.
 As water enters the pump, it increases the volume in the salt chamber,
creating pressure within the pump.
 This pressure compresses the flexible reservoir, forcing the drug solution to be
delivered through the exit port of the pump.
 The drug or hormone is thus released into the animal's body at a controlled
and continuous rate.