ORAL DRUG DELIVERY

Dr. Budipratiwi W., S.Farm., MSc., Apt.

FAKULTAS FARMASI UNIVERSITAS JEMBER

 Oral Drug Delivery

Preferential route of administration

 Simple and most economical

 Most convenient CHALLENGES
 non-invasive and safe

Improvements in oral drug delivery technology

2
 Swallowing difficulty
 Irritant and unpalatable drugs
 GI destruction of labile molecules
 Low level of macromolecular absorption
 Slow onset of action
 Very little control over release of the drug
 Non-specific delivery site
 Dosing frequency
 I. Ease of Administration
A. Oral Disintegrating Tablets (ODT)
 Fast Dissolving Tablets (FDT) = Fast-melt = Fas
disintegrating
 Tablets with optimal mechanical strength and
disintegrating within 60 seconds in the oral cavity
 I. Ease of Administration
B. Oral Controlled Release Drug Delivery
Systems (OCRDDS)
 Reduce dosing frequency, improved patient
compliance and reduce level of local or systemic
side effects
 Increase the safety margin (better control of
plasma levels), increase bioavailability
 LEADS to shorter treatment period → Reduction in
health care cost
 OCRDDS design to:
a. Deliver an initial burst of a drug for fast
therapeutic effects, followed by controlled release
at a constant rate
b. Deliver a drug to specific sites within patient’s GIT

 By constructing a multilayered tablet having a water

soluble/ swelling as well as erosion occurs
simultaneously → contributes to the drug release
 Using polymer matrix such as: HPMC, Povidone
II. DEVELOP GASTRIC RETENTION
 Needed for API:
 Locally active in the stomach
 Have an absorption window in the stomach or
in the upper small intestine
 Unstable in the intestinal environment
 Exhibit low solubility at high pH values

 Gastro-Retentive Drug Delivery (GRDD)

1) Altering API particles density
2) Using muco-adhesive polymers
3) Altering the size of dosage form
 1) Altering API particles density
a. Drug pellets having density higher than GI fluid
density (1.4 g/cc), preferable above 1.6 g/cc
 The drug is covered on the heavy core and then covered by
a diffusion controlled membrane
 Using iron oxide, titanium dioxide, and barium sulphate

b. Drug pellets having density less than that of GI

fluids (Low density pellets)
 Hydro-dynamically balanced system, float on the gastric
fluid for an extended time while slowly releasing the drug
 Impregnating a water miscible liquid (glycerol, sodium
chloride) in the lipophilic matrix
 A gas filled flotation chamber can be attached to a
membrane coated tablet for making it buoyant
 Using HPMC, HEC, HPC, lipophilic polymers (silicon
elastomer)
2) Using muco-adhesive polymers
 Drug retention in the stomach membrane achieved
using microspheres based mucoadhesive formulation
 Microsphere system  sustained release drug;
mucoadhesive system  good mucoadhesion between
drug matrix and stomach mucosa
 Polymer used: Chitosan, Thiolated Chitosan, Carbopol,
and Methocel

3) Altering the size of dosage form

 Dosage form 2.5 mm size  delayed emptying time
 Disadvantages  difficult to swallow
III. Small Intestine Delivery  Formulation of
Poorly Soluble and High Molecular Weight API
A. Enhancing Delivery of Poor Water Soluble API
1. Solid Dispersion
2. Microemulsions
3. Self-Emulsifying Systems
B. Solid Self-Nanoemulsifying Systems (SSNES)
C. Nano and Micro-particle Approach
D. Enhancing Delivery of BCS class 3 API
E. Delivery of Proteinous Drugs
A. Enhancing Delivery of Poorly Water Soluble Drugs
I. Solid dispersion
The dispersion of one or more API in an inert carrier or matrix
in solid state that can be prepared by various method such as:
a. Melting method
b. Solvent methods
c. Melting solvent method (melt evaporation)
d. Melt extrusion methods
e. Lyophilization techniques
f. Melt agglomerations Process
g. The use of surfactant
h. Electro spinning
i. Super Critical Fluid (SCF) technologies
 Based on their molecular arrangement, solid dispersion can be
classified as:
Type1- Simple eutectic mixture
Type2-Amorphous precipitations in crystalline matrix
Type3-Solid solutions
Type4-Glass suspension
Type6-Glass solution
• Matrix components: PEG, Povidone, Poloxamer, HPMC,
crystalline urea, other polymer
II. Microemulsion
 Liquid dispersions of water and oil
 Homogenous, transparent, thermodynamically stable
 Stabilize by a surfactant, usually in combination with a co-
surfactants
III. Self-Emulsifying System (SEDDS)

 Emulsify spontaneously to produce fine oil-in-water

emulsion when introduced into an aqueous phase
under gentle agitation and spread readily in the GIT
 SEDDS spread readily in the GIT and the digestive
motility of the stomach and the intestine provide
the agitation necessary for self-emulsification
 Occurs when the entropy change that favors
dispersion is greater than the energy required
to increase the surface area of the dispersion
 Comprises a hydrophilic surfactant with HLB value
greater than 10.
 Can improve bioavailability of BCS class 2 API
 B. Solid Self-Nanoemulsifying Systems (SSNES)
 Combines the advantages of liquid SNEDDS with those of
a solid dosage form and overcomes the limitations
associated with liquid formulations
 S-SNEDDS also exhibited more commercial potential and
patient acceptability
 Many techniques are offered to convert conventional
liquid SNEDDS to solid form such as spray drying,
adsorptions to solid carriers, spray cooling, melt
extrusion, melt granulation, supercritical fluid based
methods and high pressure homogenization.
 The resulting powder may then be filled directly into hard
gelatin capsules or mixed with suitable excipients before
compression into tablets.
 C. Nano and Micro-particle Approach
 A decrease in particle size  increased surface area 
faster dissolution  increase in bioavailability
 Breaking down API’s crystal lattice → API nanocrystals
and or amorphous API → stabilize with biologically inert
and biocompatible carriers → disperse in GIT fluids
 Particle engineering technology:
 Controlled Precipitation
 Template Emulsion
 Spray Freezing into Liquid (SFL)
 Evaporative Precipitation into Aqueous Solution (EPAS)
• Polymeric nanoparticles and Nanoparticles-in-
microsphere oral system (NiMOS)
Pure nanoparticles (poorly water-soluble), encapsulated
within mucoadhesive microparticles to increase its oral
bioavailability
These microparticles : not stable in the gastric fluids → re-
encapsulated within gastro-resistant capsules to prevent
disintegration and fast drug release in the stomach
 D. Enhancing Delivery of BCS class 3 API
 BCS class 3 API????
 Lipid base carriers  optimal absorption of the API
across the epithelial cell membranes of the intestinal tract
 The technology enables oral delivery of API that are
currently delivered only by invasive route
(polysaccharides, peptides, genetic materials, cytokines,
and protein)
 E. Delivery of Proteinous Drugs
 Major challenge : vast number of functional groups that
can undergo chemical degradation
 Creating a suitable and stable oral dosage form of
therapeutic protein  microparticles of protein,
polypeptide and peptide drugs
 TECMs (Thiolated Eudragit-coated CMs)  loaded with
BSA (bovine serum albumin)
 Eligen® technology
 Enable therapeutic macromolecules transport across biological
GIT membrane, without altering its chemical integrity
 Allowing the therapeutic molecules to exert their desire
pharmacological effect
 Molecule size : 500 to > 150.000 Dalton
IV. Targeting to the Colon
Objectives:
1. To reduce dosing frequency
2. To achieve high local concentration of API in the
treatment of distal gut disease
3. To delay delivery to a time appropriate to treat
acute phases of disease (chronotherapy)
4. To deliver API to a region that is less hostile
metabolically
Common Approaches used for Colon Targeting

A. Prodrug
B. pH Controlled System/ Colon Targeting by Coating
C. Matrix Based System
D. Time-Delayed System
E. Colon-Specific Swell-able (Biodegradable) Polymers
F. Pressure Controlled Delivery
G. Osmotic Controlled Delivery
H. Pulsincap system