INTRODUCTION 　　Conventional oral drug delivery systems are known to provide an immediate release of drug, in which one cannot control the release of the drug and effective concentration at the target site. The bioavailability of drug from these formulations may vary significantly, depending on factors such as physico-chemical properties of the drug, presence of excipients, various physiological factors such as the presence or absence of food, pH of the GI tract, GI motility, etc. so to overcome this limitation oral route is replied by parenteral route. This route offers the advantage of reduced dose, targeting of site and avoiding GI stability, hepatic by-pass of drug molecule. (1) 　　In recent years, much attention has focused on novel drug delivery systems (NDDS). There are many designing options available to control or modify the drug release from a dosage form. Numerous technologies have been used to control the systemic delivery of drugs. Based on the mechanism of the drug release can be classified as: Diffusion controlled (matrix and reservoir type of systems) Dissolution controlled (surface eroding, surface swelling type of systems) Osmotic drug delivery Multi particulate systems Enteric coated (pH dependent systems) 　　One of the most interesting one is that employs osmotic pressure as an energy source for release of drugs. 　　The role of drug development is to take a therapeutically effective molecule with sub-optimal physicochemical and/or physiological properties and develop an optimized product that will still be therapeutically effective with additional benefits such as: Sustained and consistent blood levels within the therapeutic window Enhanced bioavailability Reduced interpatient variability Customized delivery profiles Decreased dosing frequency Improved patient compliance Reduced side effects. 　　　　Osmotically controlled oral drug delivery systems (OCODDS) utilize osmotic pressure as the energy source for the controlled delivery of drugs. Drug release from these systems is independent of pH and hydrodynamic conditions of the gastro-intestinal tract (GIT) to a large extent and release characteristics can be easily adjusted by optimizing the parameters of the delivery system. PRINCIPLE 　　　　The flow of solvent depends on SPM characteristics and different osmosis pressures between two sides of regions. 　　　　Osmosis pressure for concentrated solution of soluble solutes commonly used in controlled release formulation are extremely high, ranging from 30 atm for sodium phosphate up to 500 atm for a lactose-fructose mixture (US patent number 4077407). These osmosis pressures can produce high water flows across semi permeable membrane. TYPES OF PUMPS Oral Osmotic Pumps Elementary osmotic pump(8) Push Pull Osmotic Pump(9) Controlled porosity Osmotic Pumps (CPOP)(10) OROS CT System(11) NEED OF THE STUDY Present investigation is to develop controlled osmotic tablet of

1. Development of Osmotically Controlled Oral Drug Delivery
Systems of Tramadol Hydrochloride: Effect of
Formulation Variables on in-vitro Release Kinetics.
By
Swapna. P
M. Pharmacy
Department of Pharmaceutics
St. Peter’s College of Pharmacy
Guide: Dr. Sunil

2. 1

3. LITERATURE REVIEW
Fig : 2
TaskerA et al. studied the use of osmotic mini pumps as alternatives for
injections for sustained drug delivery in adult rats.
Lee HB et al. studied the sandwiched osmotic tablet system (SOTS), for the
purpose of delivering nifedipine.
2

4. DRUg pRofILE (Tramadol hydrochloride)
 It belongs to Class I of BCS classification
 Pharmacokinetic data:
 Protein binding: 20%
 Bioavailability: 68- 72%
 Metabolism: Hepatic Demethylation and
Glucuronidation.
 Half-life: 5.5 to 7hrs.
 Excretion: Renal Excretion.
 Melting point: 180-181ºc.
 Dose: 3–4 times a day.
 Uses:
 Centrally acting Opioid Analgesic
Fig:3 Structure of TRAMADOL. HCl
(C16H26ClNO2)
3

5. SOLVENT TRAMADOL HCl
Water Highly soluble
Methanol Soluble
Ethanol Soluble
Chloroform Sparingly soluble
DMSO Sparingly soluble
0.1N HCl Soluble
6.8pH buffer Soluble
7.4 pH buffer Soluble
SoLUbILITy STUDIES of DRUg
Table: 4
4

6. EXCIpIENTS
 Talc
 Magnesium Stearate
 PVP K-30
 PEG 400
 Ethanol anhydrous
 Micro crystalline cellulose
 Potassium Chloride
 Mannitol
 Cellulose acetate
 Acetone
 Triethyl citrate
 Castor Oil
Lubricants
Diluents
Osmogens
Coating polymers
5

7. Types of oral osmoTic pumps
 Elementary osmotic pumps
 Push pull osmotic pumps
 Controlled porosity osmotic pumps
 OROS- CT system
Fig : 3 6

8. INGREDIENTS
FORMULATION CODE
F1
(1:0)
F2
(1:0.5)
F3
(1:0.75)
F4
(1:1)
F5
(1:1.25)
Tramadol HCl 100 100 100 100 100
KCl(osmogen) 0 50 75 100 125
MCC 135 85 60 47.5 10
PVP 12.5 12.5 12.5 12.5 12.5
Mg.Stearate 2.5 2.5 2.5 2.5 2.5
Iso propyl alcohol q.s q.s q.s q.s q.s
USING KCl AS OSMOGEN DIFFERENT RATIO OF
DRUG :OSMOGEN
formulaTion of osmoTic pump TaBleTs
(Core Tablets)
Table: 1
7

9. INGREDIENTS
FORMULATION CODE
F6
(1:0)
F7
(1:0.5)
F8
(1:0.75)
F9
(1:1)
F10
(1:1.25)
Tramadol HCl 100 100 100 100 100
Mannitol
0 50 75 100 125
(osmogen)
MCC 135 85 60 47.5 10
PVP 12.5 12.5 12.5 12.5 12.5
Mg.Stearate 2.5 2.5 2.5 2.5 2.5
Iso propyl alcohol q.s q.s q.s q.s q.s
USING MANNITOL AS OSMOGEN DIFFERENT RATIO OF
DRUG:OSMOGEN
formulaTion of osmoTic pump TaBleTs
(Core Tablets)
Table: 2
8

10. sTeps involved in preparaTion
Formulation of core tablet
Coating Of Core Tablet (Perforated
Coating Pan)
Drilling Of Coated Tablets (Microdriller)
(400μm,800μm,1200μm)
Evaluation of the osmotic pump tablets
Fig: 4
9

11. INGREDIENTS CONCENTRATION WEIGHT
Composition of coating solution
formulaTion of osmoTic pump TaBleTs
(Coating Solution)
Cellulose
acetate
4% 40gms
Triethyl citrate 0.4% 4gms
Acetone Q.S 1000ml
Castor oil 2%w/v of cellulose
acetate
0.8ml
Table: 3
10

12. Formulation
Code
B D
(gm/cm3)
(n=3)
Mean ±S.D.
TD (gm/cm3)
(n=3)
Mean ± S.D.
Hausner’s
Ratio
Carr’s Index
Angle of
Repose
(n=3)
Mean ±S.D.
Loss on
Drying(%)
F1 0.35±0.006 0.39±0.006 1.12 10.34 25.68±0.069 1.21
F2 0.36±0.006 0.41±0.006 1.12 10.66 25.61±0.102 1.10
F3 0.37±0.010 0.41±0.006 1.10 09.02 26.45±0.049 1.12
F4 0.35±0.006 0.40±0.000 1.13 11.67 25.48±0.045 1.13
F5 0.36±0.015 0.40±0.006 1.09 08.40 26.18±0.142 1.10
F6 0.36±0.006 0.40±0.006 1.13 11.57 27.23±0.107 1.11
F7 0.37±0.006 0.42±0.006 1.12 10.40 25.92±0.057 1.15
F8 0.36±0.006 0.40±0.010 1.12 10.83 26.70±0.053 1.21
F9 0.37±0.010 0.41±0.000 1.11 09.76 25.39±0.070 1.15
F10 0.36±0.010 0.40±0.006 1.11 10.00 27.14±0.066 1.20
Table: 5 Pre-Compression Evaluation of Osmotic Pump Tablets
11

13. Post Compression Evaluation of Osmotic Pump Tablets
Formulation
code
Thickness(mm)
(n=3)
Average(mg
)weight(n=3
)
Hardness (kg/cm2)
(n=10)
Friability Content
uniformity
Before coating After
coating
Before
coating
After
coating
Before
Coating
F1 4.22±0.01 4.42±0.12 250±0.01 5.1±0.09 7.2±0.01 0.01±0.01 99.3±1.69
F2 4.24±0.10 4.44±0.26 251±0.01 5.1±0.10 7.3±0.01 0.01±0.12 99.8±0.37
F3 4.21±0.06 4.41±0.02 249±0.02 5.0±0.05 7.0±0.02 0.01±0.15 100.1±1.94
F4 4.20±0.15 4.40±0.01 250±0.01 5.1±0.10 7.4±0.02 0.05±0.06 99.8±0.47
F5 4.23±0.01 4.43±0.01 250±0.01 5.0±0.01 7.2±0.06 0.03±0.20 99.5±0.19
F6 4.22±0.06 4.42±0.06 249±0.06 5.1±0.11 7.3±0.01 0.04±0.22 99.8±1.29
F7 4.24±0.15 4.44±0.02 250±0.15 5.1±0.04 7.3±0.05 0.03±0.06 100.0±1.02
F8 4.21±0.06 4.41±0.01 251±0.02 5.0±0.03 7.3±0.04 0.01±0.03 100.3±1.46
F9 4.22±0.01 4.42±0.06 251±0.02 5.0±0.02 7.2±0.06 0.02±0.13 99.5±0.41
F10 4.23±0.01 4.43±0.01 250±0.01 5.1±0.09 7.0±0.02 0.03±0.01 99.3±0.76
Table: 6
12

14. % Drug Release of all core tablet formulations
Fig.6: Effect of Osmogen (Mannitol)
Concentration on In-vitro Drug
Release
Fig.5: Effect Of Osmogen (KCL)
Concentration On In-vitro Drug Release
13

15. Fig : 7 % Drug Release of all coated formulations
F4C showed controlled drug release of about 90.9% in 24hrs
14

16. Formulation
code
Zero
order(R2)
First
order(R2)
Higuchi(R2) Peppas (n)
F1C 0.978 0.749 0.902 0.864
F2C 0.964 0.605 0.889 0.735
F3C 0.965 0.655 0.821 0.75
F4C 0.994 0.805 0.962 0.895
F5C 0.988 0.844 0.987 0.788
Table: 7
ORDER OF DRUG RELEASE KINETICS
15

17. FT-IR STUDIES
Fig.8: FT-IR SPECTRA OF PURE
DRUG (TRAMADOL HCl)
Fig.9: FT-IR SPECTRA OF
OPTIMIZED FORMULATION (F4)
16

18. Fig.10: Pure drug Fig.11: Core tablet
Fig.12: Coated tablet
17

19. discussion
18

20. 19

21. bibliography
1. Das N. and Das S. Controlled Release of Oral Dosage Forms
Formulation. Fill & Finish; 2003; p.10-5.
2. Vyas SP, Khar RK. Controlled drug delivery concepts and
advances; osmotically regulated systems, 1st edition, p.477-
501.
3. Jain NK. Advances in Novel and Controlled Delivery. 2002;
p.18-39.
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22. 21
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