It includes information about oral, pulsatile, Colon, Gastroretentive drug delivery systems....

1. ORAL DRUGORAL DRUG
DELIVERYDELIVERY
SYSTEMSYSTEM
Presented By-
Musale Baliram Sugriv
M. Pharmacy Ist year
(Pharmaceutics)
1

2. Oral controlled release systemOral controlled release system
Oral route has been most popular & successfully
used route for controlled delivery of drugs because
of following reasons-
Convenience & ease of administration.
Greater flexibility in dosage form design.
Ease of production & low cost of such a system.
2

3. • An oral CDDS can be designed as-
• CONTINUOS RELEASE SYSTEM– release drug
continuously over an extended period of time.
• PULSATILE RELEASE SYSTEM– are characterized
by a time period of no release followed by a rapid
& complete or extended drug release.
3

4.  CONTROLLED RELEASE ORAL FORMULATION
A.CONTINUOUS RELEASE SYSTEMS B. PULSED RELEASE SYSTEM
1.CONTINUOUS TRANSIT SYSTEM 1.TIME SPECIFIC SYSTEM
MATRIX OSMOTIC PRESSURE
RESERVOIR RUPTURABLE COATING
ORAL OSMOTIC SWELLABLE COATING
ION-EXCHANGE RESINS DIFFUSIVE COATING
PULSINCAP
2. GASTRORETENTIVE SYSTEM 2.COLON SPECIFIC SYSTEM
LOW DENSITY SYSTEM TIME
HIGH DENSITY SYSTEM PH
MODIFIED SHAPE SYSTEM TIME/PH DEPENDENT
MUCOADHESIVE SYSTEM ENZYME
OSMOTIC PRESSURE
4

5. Matrix type oral CDDSMatrix type oral CDDS
Are possibly the most common of monolithic
devices for controlling the release of drugs for
following reson-
1. Easy of fabricate compared to reservoir
2. No danger of accidental dose dumping
compared to monolithic reservoir.
In such device active agent present as dispersion
within polymer matrix. & formed by compression of
polymer/ drug matrix or by melting
5

6. Conventional matrix tablet designConventional matrix tablet design
6

7. Reservoir type oral CDDSReservoir type oral CDDS
Are those where the drug crystal, particle, granule,
pellet ,minitablet or tablet is present as core
encapsulated with a rate controlling wall,
film/membrane having a well defined thickness.
Drug release occurs predominantly by diffusion.
Advantage of such system –
 zero order delivery is possible
 Release rate modulated by polymer type, polymer
membrane thickness, & membrane porosity.
Disadvantage- higher cost of formulation.
7

8. Reservoir pellet design for oral drugReservoir pellet design for oral drug
deliverydelivery
8

9. Oral osmotic (OROS) CDDSOral osmotic (OROS) CDDS
Based on diffusion & erosion, osmotic system are
more complex in design but provide better zero-
order drug delivery.
They work on principle of osmotic pressure to
release the drug at a constant zero-order rate.
9

10. In design OROS system compries of 4 basic component
1.A rigid shape retaining semipermiable
membrane(SPM) that surrounds drug/ osmogent core
2.A drug layer
3. Osmogent –that embites water & generates osmotic
pressure that drives dispersed drug through delivery
orifice.
Commonly used osmogent are sodium chloride,
dextrose, mannitol. Swellable osmopolymer include
PEO, HPMC.
4.Delivery orifice which is generally laser-drilled into
semipermeable membrane.
10

11. GASTRORETENTIVEGASTRORETENTIVE
DRUG DELIVERYDRUG DELIVERY
SYSTEMSYSTEM
11

12. 12
• INTRODUCTION
• APPROPRIATE CANDIDATE DRUGS FOR
GRDDS
• ADVANTAGES
• LIMITATIONS
• APPROACHES
• EVALUATION TEST
CONTENTS

13. 13
INTRODUCTION
• Oral drug delivery is widely used in pharmaceutical
field to treat the diseases.
• Some drugs are absorbed at specific site only ,these
require release at that specific site.
• Gastro retentive drug delivery(GRDDS) is one of the
site specific drug delivery for the delivery of the drugs
at stomach.
• It is obtained by retaining dosage form into stomach
and drug is being released at controlled manner at
specific site

14. 14
APPROPRIATE CANDIDATE
DRUGS FOR GRDDS
• Drugs acting locally in the stomach.
E.g. Antacids and drugs for H. Pylori viz.,
Misoprostol.
• Drugs that are primarily absorbed in the stomach.
E.g. Amoxicillin
• Drugs that is poorly soluble at alkaline pH.
E.g. Furosamide, Diazepam, Verapamil, etc.
• Drugs with a narrow absorption window.
E.g. Cyclosporine, , Levodopa, Methotrexate

15. Drugs which are absorbed rapidly from the GI tract.
E.g. Metronidazole, tetracycline.
Drugs that degrade in the colon.
E.g. Ranitidine, Metformin.
Drugs that disturb normal colonic microbes
E.g. antibiotics against Helicobacter pylori.
15

16. 16
ADVANTAGES
• Enhanced bioavailability
• Sustained drug delivery reduced frequency of
Dosing
• Targeted therapy for local ailments in the upper GIT
• Reduced fluctuations of drug concentration
• Improved selectivity in receptor activation
• Reduced counter-activity of the body
• Extended effective concentration
• Minimized adverse activity at colon

17. 17
LIMITATIONS
• The drug substances that are unstable in the acidic
environment of the stomach are not suitable candidates to
be incorporated in the systems.
• These systems require a high level of fluid in the stomach
for drug delivery to float and work efficiently.
• Not suitable for drugs that have solubility or stability
problem in GIT.
• Drugs which are irritant to gastric mucosa are also not
suitable.
• These systems do not offer significant advantages over the
conventional dosage forms for drugs, which are absorbed
throughout GIT.
17

18. 18
APPROACHES FOR PROLONGING
THE GASTRIC RESIDENCE TIME
F
S
HD
S
A
S
S
S
18
• High-density systems.
(HDS)
• Floating systems. (FS)
• Swelling and expanding
systems. (SS)
• Mucoadhesive &
Bioadhesive systems.
(AS)
F
S
HD
S
A
S
S
S

19. Classification of GRDDSClassification of GRDDS
1.LOW DENSITY SYSTEM/ FLOATING DOSAGE
FORM
a) Effervescent system /Gas generating system
b) Non-effervescent systems
Sweling/expanding system
Inherently low density system
2.HIGH DENSITY SYSTEM
3. MODIFIED SHAPE SYSTEM
4. MUCOADHESIVE SYSTEM
19

20. 1. LOW DENSITY SYSTEM/ FLOATING1. LOW DENSITY SYSTEM/ FLOATING
DOSAGE FORMDOSAGE FORM
 Prepared by incorporating a high level(20-75%w/w)
gel-forming hydrocolloids. E.g.:-
Hydoxyethylcellulose, hydroxypropylcellulose, HPMC
& Sod. CMC into the formulation and then
compressing these granules into a tablets or capsules.
 It maintains the bulk density less than 1
20

21. Have a bulk density less than gastric fluid & so
remain buoyant in stomach called as
HYDRODYNAMICALY BALANCED SYSTEM
21

22. a. Effervescent / Gas generating system
It increases size of drug delivery system as well
as decrease its density & provides floating
properties
This system formulated as matrices / resinate.
Following are types of gas generating GRDDS
Conventional matrix tablets
Layered matrix tablets
Core coated tablet
Ion-exchange resin complexs
22

23. • GAS GENERATING SYSTEM
Carbonates or bicarbonates, which react with
gastric acid or any other acid (e.g., citric or
tartaric) present in the formulation to produce
CO2 , are usually incorporated in the dosage
form, thus reducing the density of the system
and making it float on the media.
23

24. b. NON-EFFERVESCENT SYSTEMb. NON-EFFERVESCENT SYSTEM
SWELLING / EXPANDING SYSTEMSSWELLING / EXPANDING SYSTEMS
These systems use a gel forming / swellable hydrocolloid
such as polysaccharides like guargum, cellulosics- HPMC,
synthetic polymers- PEO, carbomer.
It consist of embedding drug powder/ pellets in gel forming
hydrocolloids.
After oral administration dosage form swell on contact with
gastric fluid
The formed swollen gel-like structure acts as reservoir &
allows sustained release of drug through gelatinous mass.
24

25. INHERENTLY LOW DENSITYINHERENTLY LOW DENSITY
SYSTEMSSYSTEMS
Two types—
a. Entrapment of air (hollow
microspheres/microballoons)
Emulsion solvent diffusion method
Modified solvent evaporation method
Dehydration of swollen hydrogel
Hollow chamber system
b. Incorporation of low density materials.
25

26. Polymers used commonly: Polycarbonates,
Cellulose acetate, Calcium alginate, Eudragit S,
agar and methoxylated pectin etc
HOLLOW MICROSPHERES
26

27. Emulsion- solvent diffusion methodEmulsion- solvent diffusion method
A solution of polymer & drug in ethanol/
methylene chloride is poured in aq. Solution of
PVA .ethanol partitions into external aq. Phase
& polymer participates around methylene
chloride droplets.Then subsequent evaporation
of entrapped methylene chloride leads to
formation of internal microcavity within
microparticles
27

28. MODIFIED SOLVENTMODIFIED SOLVENT
EVAPORATION METHODEVAPORATION METHOD
Drug powder is dispersed into solution of cellulose
acetate butyrate & eudragit RL 100 in acetone.
The dispersion pressurised under CO2 gas , which
dissolves & forms bubbles following the release of
pressure.
Generated CO2 bubbles are entrapped within dispersed
drug-polymer droplets & leads to formation of
internal cavities within hardened microsphers.
28

29. DEHYDRATION OF SWOLLEN HYDROGELDEHYDRATION OF SWOLLEN HYDROGEL
System consist of hydrated drug loaded calcium
alginate core, which is coated with PVA membrane
.Drying of hydrogel result in formation of air
compartment owing to shrinkage of hydrated core
HOLLOW CHAMBER SYSTEM
These system prepared by coating drug on hollow core
such as poprice , empty gelatin capsules / polystyrene
beads followed by coating the drugs with rate-
controlling membrane
29

30. • Prepared by dropping sodium
alginate solution into aqueous
solution of calcium chloride,
causing the precipitation of
calcium alginate
• Freeze dry in liquid nitrogen at
-40o
c for 24h.
• Beads-spherical and 2.5 mm
Swellable agents have pore
size ranging between 10nm to
10µm.
Superporous hydrogels will
swell more than the swelling
ratio 100,This is achieved by
co-formulation of a hydrophilic
particulate material, and Ac-Di-
Sol (crosscarmellose).
ALGINATE BEADS SUPERPOROUS HYDROGELS
30

31. LOW DENSITY MATERIALSLOW DENSITY MATERIALS
Fats & low density polymers used to prepare
floating drug matrices.e.g. Polypropylene foam
powder ,matrix-forming polymers ,drug & an
optional filler.
Polypropylene foam powder based drug
microparticals prepared by soaking microporous
foam particals in organic solution of drug &
polymer.
31

32. 2. HIGH DENSITY2. HIGH DENSITY
SYSTEMSYSTEM
Density of system is larger than gastric
juice (>1.4 g/ml) , the device settles down
to bottom of stomach , remaining located
below the pylorus.
Iron oxide , titanium dioxide & barium
sulphate used to increase density of drug
pellets.
The drug is coated on heavy core & then
covered by diffusion controlled membrane.
The approach is not very successful.
32

33. 3. MODIFIED SHAPE SYSTEM / UNFOLDING3. MODIFIED SHAPE SYSTEM / UNFOLDING
SYSTEMSYSTEM
These system consist of atleast one erodible polymer ,
one non-eroidible polymer & drug that is dispersed
within polymer matrix.
Drugs incorporated in several geometric shapes such as
tetrahedron, ring, disc, spiral, pellet/ sphere which can
be packed into gelatine capsule & unfold after
dissolution of capsule shell.
33

34. 4. BIOADHESIVE SYSTEMS / MUCOADHESIVE SYSTEM4. BIOADHESIVE SYSTEMS / MUCOADHESIVE SYSTEM
Bioadhesive polymer e.g. carbomer, chitosen used
to coat dosage form so that it adheres to gastric
mucosa.
Adv.is –in stomach is intimate contact with mucosa
leading to short pathways for locally acting drugs
such as antibiotics against
H. pylori.
34

35. Marketed productMarketed product
BRAND NAME ACTIVE INGREDIENT
Cifran OD Ciprofloxacin
Madoper L-DOPA,benserazide
Valrelease Diazepam
Topalkan Aluminium mg.antacid
Almagate flat coat Aluminium mg. antacid
35

36. EVALUATIONTESTS:EVALUATIONTESTS:
Evaluation of tabletsEvaluation of tablets
Buoyancy lag timeBuoyancy lag time
In vitro dissolution behaviourIn vitro dissolution behaviour
Swelling indexSwelling index
Hardness & friabilityHardness & friability
Weight variationWeight variation
Evaluation of microspheres & beadsEvaluation of microspheres & beads
Particle size analysisParticle size analysis
Surface characterizationSurface characterization
In vivo evaluation (Gamma scientigraphy)In vivo evaluation (Gamma scientigraphy)
36

37. Buoyancy lag time & duration ofBuoyancy lag time & duration of
buoyancybuoyancy
The buoyancy lag time & duration of buoyancy
determined in USP dissolution apparatus II in
acid enviornment.
The lag time interval between introduction of
tablet into dissolution medium & its buoyancy
to top of dissolution medium was taken as
buoyancy lag time / floating lag time & duration
of buoyancy was observed vissually.
37

38. In vitro dissolution behaviourIn vitro dissolution behaviour
Release of medicament studied by USP II type
dissolution apparatus (paddle type) dissolution
performed at predetermined speed & temperature
37±0.5ºc in appropriate dissolution medium.
5mL sample withdrawn at predetermined interval .
Absorption of withdrawn sample measured
spectrophotometrically with with suitable dilution &
corresponding concentration determined from
calibration curve.
38

39. Swelling indexSwelling index
Tablet weigh individually (W0) & placed in
dissolution medium’
Temperature maintain at 37±0.5ºc
At regular interval sample removed & swollen
weight (Wt) of each determined at predefined
time interval
% swelling index =Wt-Wo /Wo x 100
Wt– weight of tablet at time t
W0– initial weight of tablet.
39

40. Hardness & friabiltyHardness & friabilty
Hardness– force applied to break tablet
Resistance of tablet to chipping, abrasion, breakage
under condition of storage, transformation, handling
before usage depends on its hardness.
Measured by using Monsanto hardness tester.
Friabilty– Roche friabilator
Take tablet in plastic chamber , revolving at 25 rpm &
dropping tablet at height of 6 inch in each
revaluation.
%Friabilty = intial wt of tab.—final wt of tab./initial wt
 of tabX100
40

41. Weight variationWeight variation
USP provides wt. variation test by weighing 20
tablet individually , calculating average wt &
comparing the individual tablet wt. To
average.
Tablet meet USP test if no more than 2 tablet
outside the % limit.
41

42. Evaluation for microspheres & beadsEvaluation for microspheres & beads
Particle size analysis
Surface characterisation
Particle size analysis- determined using optical
microscopy
Surface characterisation- determined using (SEM)
scanning electron microscopy
42

43. In vivo evaluation (GammaIn vivo evaluation (Gamma
scientography)scientography)
This method helps to locate dosage form in GI
tract by which we can predict & correlate
gastric emptying time & passage of dosage
form in GIT.
Gamma rays are emitted by nucleotide are
focused on camera , which helps to monitor
the location of dosage form in GI tract.
43

44. COLON TARGETED
DRUG DELIVERY
SYSTEM
44

45. INTRODUCTIONINTRODUCTION
The most useful drug delivery system to treat
colonic disorder & colon cancer are failing due to
inappropriate concentration of drug that do not
get to the site of action.
Colon targeted drug delivery system are suitable
site for absorption of peptides & proteins.
The CDDS highly desirable for local treatment of
variety of bowl diseases such as ulcerative colitis,
crohn’s disease,colonic cancer.
45

46. 46
Promising site for drug delivery
Local disorders
Systemic absorption
oDrugs unstable in upper GIT
oDrugs poorly absorbed from GIT
oDrugs that necessitate targeting at site
Colon as a site for drug delivery

47. Advantages of Colon TargetedAdvantages of Colon Targeted
drug delivery systemdrug delivery system
Drug directly reaches the target site.
It reduces dose of drug to be
administrated.
It minimizes side effect
It enhances drug utilization.
47

48. Anatomy & Physiology of colonAnatomy & Physiology of colon
GI tract is divided into –
Stomach
Small intestine
Large intestine
The large intestine extend
from ileocaecal junction to
anus which is divided into 3
main parts-colon, rectum,
anal canal.
48

49. Colon itself consist of –
Caecum (Asending colon)
Hepatic flexure (Transvers colon)-longest
Splenic flexure (Descending colon)
Sigmoidal colon
The wall of colon composed of 4 layers
Serosa
Muscularis externa
Sub-mucosa
Mucosa
49

50. Function of colonFunction of colon
Formation of suitable environment for colonic
microorganism.
Act as storage reservoirs of waste matter.
Removal of content of colon at proper time.
Absorption of potassium ion & water from
lumen, concentrating fecal content &
secretion & excretion of potassium &
bicarbonates.
50

51. GastrointestinalTransit --
Gastric emptying of various dosage form is highly
inconsistant & depends primary on whether the subject
is fed or fasting & properties of dosage form.
The arrival of dosage form in colon is determined by
rate of gastric emptying & intestine transit time.
Intestinal transit time
Organ Transit time (hrs)
Stomach <1 (fasting)
>3 (fed)
Small intestine 3-4
Large intestine 20-30
51

52. 52
Ulcerative colitis
 Inflammatory bowels disease (IBD)
Crohn’s disease
Colonic polyps
Colorectal cancer
Others as amebiasis, diarrhoea etc
Disorders of Colon

53. Criteria Pharma -
cological
class
Nonpeptide
drug
Peptide
drug
Drug used for
local effect in
colon against
disease
Anti-
inflammatory
drugs
Oxyprenolol
Metoprolol
Nifedine
Amylin
Antisense
oligonucleotide
Drugs poorly
absorbed from
upper GIT
Antihypertensiv
e
Antianginal
drugs
Ibuprofen
Isosorbides
Theophylline
Cyclosporine
Desmopressine
Drugs for colon
cancer
Antineoplastic
drugs
Psedoephedrine Epoetin
Glucagon
Drugs that
degrade in
stomach & small
intestine
Peptides &
proteins
5-florouracil
Doxorubicin
Gonadoreline
Insulin
53

54. Approach for colon targetedApproach for colon targeted
drug delivery systemdrug delivery system
Following approaches used for CDDS .
1. By using pH sensitive polymer.
2.Time controlled release drug delivery system
for colon.
3. Microbially controlled system for colon.
a) Prodrug
b) Azo-polymeric prodrug.
c) Polysaccharide based delivery system.
4. Osmotically controlled drug delivery system
54

55. Oral administration /
Colon targeted dosage form
Remain intact in stomach
Remain intact in small lntestine
Drug release in colon
High intracolonic drug conc.
Dose reduction
Improved efficacy
APPROACHES OF CDDS
Oral administration/
conventional dosage form
Absorption of drug either in
stomach / small intestine
Low intracolonic drug conc.
Large dose requried
Poor efficacy
Low therapeutic index
Side effect
55

56. GI TRACT SEGMENT PH
STOMACH 1-3
SMALL INTESTINE 5-7.5
LARGE INTESTINE 6.8-7.8
RECTUM 7.8-8
1. By using pH sensitive polymer1. By using pH sensitive polymer
The polymer which are pH depended in colon
targeted drug delivery are not suitable at low pH level
but become progressively more soluble as pH
increase.
Although these pH dependent polymers can protect a
drug moiety in stomach from acidic environment.
56

57. Mechanism of action of a pH dependent
system for targeted drug delivery to the
colon
pH sensitive
polymer +
drug core
DRUG
CORE
Colonic pH
Release of drug in
Colon
57

58. Sr.
No.
Polymer Threshold
pH
1 Eudragit® L 100 6.0
2 Eudragit® S 100 7.0
3 Eudragit® L –30D 5.6
4 Eudragit® FS 30D 6.8
5 Eudragit® FS 30D 5.5
6 Polyvinyl acetate phthalate 5.0
7 Hydroxy propyl methyl cellulose
phthalate
4.5-4.8
8 Cellulose acetate trimelliate 4.8
9 Cellulose acetate phthalate 5.0
Polymer of
methacryli
c acid are
mostly
used
58

59. 2.Time controlled release drug delivery system for2.Time controlled release drug delivery system for
coloncolon
Time controlled release system (TCRS) such as
sustained release dosage form are also very
promising drug delivery system.
 However due to potentially large variation of gastric
emptying time of dosage form in humans, in these
approaches, colon arrival time of dosage forms can
not be accurately predicted, resulting in poor
colonical availability.
The dosage form may also be applicable as colon
dosage forms by prolonging the lag time of about 5-6
hr.
59

60. » Releases the drug after a predetermined lag time
» The lag time usually starts after gastric emptying
because most of the time-controlled formulations
are enteric coated.
» Drug release from these systems is not pH
dependent
60

61. Lag Phase
of 5 hrs.
obeserved
61

62. Disadvantage of these system are-
1. Gastric emptying time varies markedly between
subjects / in manner dependent on type & amount of
food intake .
2. Gastrointestinal movement , specially peristalsis
or contraction in stomach result in gastrointestinal
transit of drug.
3. Accelerated transit through different regions of
colon has been observed in patients with IBD ,
carcinoid syndrome & ulcerative colites
62

63. 3. Microbially triggered drug delivery to colon3. Microbially triggered drug delivery to colon
The microflora of colon consist mainly of anaerobic
bacteria e.g. bacteroides , bifidobacteria, enterococci,
entrobacteria..etcThis vast microflora fulfil it’s energy
needs by fermenting various types of substrates that
have been left undigested in small intestine, e.g. di & tri
saccharides , polysaccharides ..etc.for this fermention,
microflra produces a vast number of enzyme like
glucoronidase, galactosidase, arabinosidase,
nitroreductase etc.
Because of presence of biodegradable enzymes only in
colon , use of biodegradable polymer for CDDS seems to
be more specific approach.
63

64. 64
Prodrugs
Drug Carrier Molecule
Enzymatic stimuli in the biological
environment of the GIT breaks the
bond
Concept
of
prodrug
s
Prodrugs
Drug Carrier Molecule
Concept
of
prodrug
s
Prodrugs
Drug Carrier Molecule
Concept
of
prodrug
s
Prodrugs
Drug Carrier Molecule
Concept
of
prodrug
s

65. a. Prodrug approach for drug delivery to colona. Prodrug approach for drug delivery to colon
Prodrug is a pharmacologically inactive derivative of
parent drug molecule that requires spontaneous
/enzymatic transformation in vivo to release active
drug.
For colonic delivery , prodrug is designed to undergo
minimal hydrolysis in upper tracts of GIT & undergo
enzymatic hydrolysis in colon there by releasing the
active drug moiety from drug moiety.
Metabolism of azo compound by intestinal bacteria
is one of most extensively studied bacterial
metabolic process.
65

66. 66
Bacteria in
colon
Hydrolysis of sulphasalazine (A) into 5-aminosalicylic
acid (B) and
sulfapyridine (C).
(
A
)
(
B
)
(
C
)

67. b. Azo polymeric new drugb. Azo polymeric new drug
In which use of polymers as drug carriers for drug
delivery to colon .
Synthetic, naturally, sub-synthetic polymers used
form colon targeted polymeric prodrug with azo
linkage between polymer & drug moiety.
The various azo polymers are evaluated for coating
materials over drug core.These are susceptible to
cleavage by azo reductase enzyme.
Coating of protein & peptide drug capsules
crosslinked with azoaromatic group Polymer to
protect drug from degradation in stomach & small
intestine. In colon azo bonds reduced & drug is
released 67

68. c. Polysaccharide based delivery systemc. Polysaccharide based delivery system
Polysaccharides offer an alternative substrate
for the bacterial enzymes present in the colon.
Most of them are hydrophilic in nature.
Natural polysaccharides are either modified or
mixed with water insoluble polymers.
68

69. 63
Polysaccharides used for Colon Drug
Delivery
• Chitosan
• Pectin
• Guar gum
• Chondroitin sulphate
• Dextran
• Cyclodextrins
• Almond gum
• Locust bean gum
• Inulin
• Boswellia gum
• Karaya gum

70. 70
Different bacterial species acting on
Polysaccharides in colon
Polysaccharides Bacterial species
Amylose
Chitosan
Chondroitin sulphate
Cyclodextrins
Dextran
Guar gum
Bacteriodes
Bifidobacterium
Bacteriodes
Bacteriodes
Bacteriodes
Bacteriodes
Bacteriodes
Ruminococccus

71. Polysaccharides Drug targeted to colon
Guar gum
Pectin
Inulin
Amylase
Cyclodextrin (β)
Dextran
Chitosan
Eudragits
Rofecoxib , Tinidazole
Naproxen
Azathioprine
5-Amino salicylic acid
Albendazole
Ibuprofen
Satranidozole
5-fluorouracil
List of few studies on
Polysaccharides
71

72. 4. Osmotically Controlled Drug Delivery
Systems
Delivery port
Osmet pump
Depend up on the osmotic pressure
exerted by osmogens on drug
compartment with which though drug
get released slowly through the
orifice.
72

73. MARKETED PRODUCTS
Sr.
no
.
Marketed
name
Company
name
Disease Drug
content
1) Mesacol tablet Sun pharma,
India
Ulcerative
colitis
Mesalamine
2) SAZO Wallace ,
India
Ulcerative
colitis,
crohn’s
disease
Sulphasalazi
ne
3) BUSCOPAN German
remedies
Colonic
motility
Hyoscine
butyl
bromide
4) Entofoam Cipla, India Ulcerative
colitis
Hydrocortiso
ne acetate
73

74. EVALUATION TESTEVALUATION TEST
In-vitro dissolution test
In-vivo test
string technique
Endoscopy technique
Gamma scintigraphy
Radiotelemetry
Roentgenography
74

75. IN-VITRO DISSOLUTIONTESTIN-VITRO DISSOLUTIONTEST
Dissolution of CDDS is usually complex, dissolution
Describe in USP
Disso. Carried out by conventional basket method.
Dissolution tests for CDDS in different media simulating pH
condition & times likely to be encountered at various
location in GI tract.
Following media were used-
pH 1.2 to simulate gastric fluid.
pH 6.8 to simulate jejunal region of small intestine.
pH 7.2 to simulate ileum segment.
Enteric coated CDDS studied in gradient disso. Study in 3
buffer systems. 2 hr at pH 1.2, then 1 hr at pH 6.8& finally at
pH 7.4
75

76. IN-VIVO METHODIN-VIVO METHOD
String method- A tablet is attached to piece of
string & subject swallows tablet, leaving free end
of string hanging from his mouth at various times.
withdrawing tablet from stomach by pulling out
the string & physically examining the tablet for
the sign for disintegration.
76

77. Endoscopy technique- It is optical tech. in which fibre
gastroscope is used to directly moniter behavior of
dosage form after ingestion
Gamma scintigraphy-
Most useful to evaluate in-vivo behavior of dosage
form in animal & humans.it requirs presence of
gamma emmiting radioactive isotopes
77

78. PULSATILE DRUGPULSATILE DRUG
DELIVERYDELIVERY
SYSTEMSYSTEM
78

79. PULSATILE DRUG DELIVERY SYSTEM
Is defined as the rapid and transient release of a
certain amount of drug molecules within a short
time-period immediately after a predetermined
off-release period.
In various diseases in which we can recomend the
pulsatile drug delivery system such as duodenal
ulcer, cardiovascular diseases, arthritis, asthma,
diabetes, neurological disorder, cancer,
hypertension and hypercholesterolemia .
79

80. 80
Pulsatile drug delivery systems (PDDS) are gaining
importance as they deliver a drug at time and site
specific manner resulting in improved therapeutic
efficacy as well as compliance.
Intelligent drug delivery system capable of
adjusting drug release rates in response to a
physiological need.

81. 81
Necessity of PDDSNecessity of PDDS
1.Chronopharmacotherapy of disease which shows
circadian rhythms in their pathophysiology-
-asthmatic attack during early morning
- heart attack in middle of night
- morning stiffness in arthritis
2. Avoiding first pass metabolism ex. Protein & peptide
3. For which tolerance is rapidly exists ex. Salbutamol
sulphate
4. For targeting specific site in intestine ex. Colon
(sulphasalazine)
5. For programmed administration of hormone & drug
6.For drug having short half-life ex. ß-blocker

82. 82
Disease Chronological behavior Drugs used
Peptic ulcer Acid secretion is high in the
afternoon and at night.
H2blockers
Attention deficit
syndrome
Increase in DOPA level in
afternoon
Methylphenidate
Cardiovascular
diseases
BP is at its lowest during the
sleep cycle and rises steeply
during the early morning
Nitroglycerin, calcium
channel,
blocker, ACE inhibitors
Asthma Precipitation of attacks during
night or at early morning.
Β2 agonist, Antihistamines
Arthritis Level of pain increases at night NSAIDs, Glucocorticoids
Diabetes mellitus Increase in the blood sugar level
after meal
Sulfonylurea, Insulin
Hypercholesterolemia Cholesterol synthesis is generally
higher during night than day
time.
HMG CoA reductase,
Inhibitors
Diseases that require pulsatile drug delivery

83. 83
Pulsatile DDS classified as-
1. Osmotic pressure release system
a.capsule/ tablet composed of large nu.of pellets
b. PORT (programmable oral release technology)
2. Reservoir system with rupturable coatings
a.Time controlled explosion system (TCES)
b. Pulsatile release tablet/compression/press-coated tablet
3. Reservoir system with swellable/soluble/erodible coating
a. Press-coated/ multilayered tablet
b. Hydrophilic sandwich capsule
c.Time clock system
d. Chronotropic system
4. Capsular system with polymeric plugs (Pulsincap)

84. 84
OSMOTIC PRESSURE RELEASE SYSTEMOSMOTIC PRESSURE RELEASE SYSTEM
a.Capsule/ tablet composed of a large number of
pellet-
Each pellet has a core that contains therapeutic drug &
water soluble osmotic agent. A water-permeable but
insoluble polymer film encloses each core.
On exposure to water , it’s penetration into pellets,
osmotic agents dissolves ,which causes pellets to swell
& drug release.

85. 85
Capsule based systems:
Single-unit systems are mostly developed in capsule
form. The lag time is controlled by a plug, which gets
pushed away by swelling or erosion, and the drug is
released as a “Pulse” from the insoluble capsule body.

86. 86
-The plug material consist of insoluble but
permeable & swellable polymers.
ex. Polymethacrylate.
-Erodible polymer- HPMC, PVA, PEO.
-Congealed melted polymer- saturated
polyglycolated glycerides, glyceryl mono-oleate
-Enzymaticaly controlled erodible polymer-pectin,
agar

87. 87
b. PORT (Programmable oral releaseb. PORT (Programmable oral release
technology)technology)
System composed of gelatin capsule coated with
SPM (ex. Cellulosic acetate) that contain immediate
release drug ,an insoluble plug (ex. Lipids) &
osmotic agent with second release of drug for
timed release.
 Upon contact with aqueous media, immediate
release drug is delivered, water enter into capsule
through SPM , which increase osmotic pressure &
result in ejection of plug after lag time , following
which second dose is delivered.

88. 88

89. 89
2. Reservoir pulsatile with rupturable coatings2. Reservoir pulsatile with rupturable coatings
These system consist of 3 layers-
1.Drug containing core .
2.Pressure generating layer- effervescent excipients
( mixture of citric acid/ tartaric acid & sodium
bicarbonate), swelling agents or osmagents .
3. Semipermeable polymer coating.
Upon contact with GI fluids, water penetrates through
polymer coating & generate pressure due to
effervescence, hydration of swelling polymer or
osmosis, then ruptures polymer coating leading to
rapid drug release.

90. 90
Examples of rupturable systemsExamples of rupturable systems
a.Time controlled explosion system
(TCES)
B. Pulsatile release tablet (PRT)/
compression/press-coated tablet.

91. 91
a.Time controlled explosion system (TCES)
It has 4 layered spherical pellet structure, consist of
inert core surrounded by a layered of drug , a swelling
agent & water insoluble polymer membrane made up
of ethylcellulose.
It is characterised by rapid drug release with
programmed lag time .
When water penetrates through polymer
membrane ,swelling agent expands, leading to
destruction of membrane with subsequent drug
release.

92. 92
Time controlled explosion systemTime controlled explosion system

93. 93
B. Pulsatile release tablet (PRT)/ compression /
press-coated tablet
It has core tablet containing a large amount of
disintigrant together with active ingredient
which is press-coated with outer shell of
ethylcellulose that controls water penetration.
When PRT administrated orally, water
penetrates through outer shell depending on
thickness & composition of coating,
disintegrant swells & collapses the outer shell
due to high swelling pressure to release the
contents as a pulse.

94. 94
Press-coated pulsatile drug delivery systems:
1.Press-coated pulsatile drug delivery systems can be used
to protect hygroscopic, light-sensitive, oxygen labile or
acid-labile drugs.
2. relatively simple and cheap.
3.These systems can involve direct compression of both
the core and the coat.
4. Materials Such as hydrophobic, hydrophilic can be used
in press-coated pulsatile drug delivery system.
5. involve compression which is easy on laboratory scale.
6. Press-coated pulsatile drug delivery formulations can be
used to separate incompatible drugs from each other or
to achieve sustained release.

95. 95
3. Reservoir system with3. Reservoir system with
swellable/soluble/erodible coatingswellable/soluble/erodible coating
In this system barrier swells, erodes / dissolves
after a specific lag period & drug is subsequently
released rapidly.
Lag time depends on thickness of coating layer.
Examples –
a. Press-coated / multilayered tablets
b. Hydrophilic sandwich (HS) capsule
c. Time clock system
d. Chronotropic system

96. 96
a. Press-coated / multilayered tablets
Press-coated system based on swelling,
disintegration or erosion mechanism for pulsatile
drug delivery.
A release pattern with two pulses obtained from a
three layered tablet conatining two drug containing
layers separated by a drug free gellable polymeric
barrier layer.
- initial rapid release drug layer
- drug-free gellable polymeric barrier layer
- second pulse generating drug layer
- impermeable ethylcellulose layer

97. 97
Multilayered tabletMultilayered tablet

98. 98
b. Hydrophilic sandwich (HS) capsule
Based on a capsule- within a capsule, in which
the inter-capsular space is filled with a layer of
hydrophilic polymer (HPMC) .
This effectively creates a hydrophilic sandwich
between the two gelatin capsules.
When outer capsules dissolves, sandwich of
HPMC forms a gel barrier layer & cause drug
release.

99. 99
c.Time clock system
Is made up of a solid dosage form, coated with a
hydrophobic surfactant layer to which a
hydrosoluble polymer is added to improve adhesion
to the core.
The outer layer redisperses in aqueous environment
in a time proportional to the thickness of film.

100. 100
d. Chronotropic system
Consist of drug containing core coated with high
viscosity HPMC which is responsible for a lag phase
in onset of release.
The lag time is controlled by the thickness and the
viscosity grades of HPMC. The system is suitable for
both tablets and capsules

101. 101
4. Capsular pulsatile system with polymeric4. Capsular pulsatile system with polymeric
plugsplugs
Example of this system is pulsincap—consist of
capsule with water soluble cap, an insoluble body
filled with drug & sealed with a hydrogel plug .
The length of plug decides lag time.
On administration, soluble cap dissolves thereby
allowing the hydrogel plug to swell & expand
After a predetermined lag time, it is swollen to an
extent that it is ejected from capsule body thereby
releasing the drug.

102. 102
PULSINCAPPULSINCAP

103. 103
The plug material consist of insoluble but
permeable & swellable polymers.
ex. Polymethacrylate.
Erodible polymer- HPMC, PVA, PEO.
Congealed melted polymer- saturated
polyglycolated glycerides, glyceryl mono-oleate
Enzymaticaly controlled erodible polymer-
pectin, agar

104. 104
Marketed technology of PDDSMarketed technology of PDDS
Technology Mechanism Brand name
& dosage
form
API Disease
pulsincapTM Rupturable
system
Pulsincap
TM
Dofetilide Hypertension
OROS Osmotic
mechanism
Covera- HS,
XL tablet
Verapamil
HCL
Hypertension

105. ADVANTAGES OF PULSATILE DRUG DELIVERY
SYSTEM:
1. Extended daytime or nighttime activity
2. Reduced side effects
3. Reduced dosage frequency
4. Reduction in dose size
5. Improved patient compliance
6. Drug adapts to suit circadian rhythms of body functions or
diseases.
7. Drug targeting to specific site
8. Protection of mucosa from irritating drugs.
9. Drug loss is prevented by extensive first pass metabolism .
10. Patient comfort and compliance: Oral drug delivery is the
most common and convenient for patients, and a reduction in
dosing frequency enhances compliance.
105

106. 106
EVALUATION OF PDDSEVALUATION OF PDDS
Weight variation
Thickness
Hardness
Friability
Wetting time
Drug content
In-vitro dissolution method

107. 107
RS