The document discusses the formulation and evaluation of pantoprazole enteric-coated tablets, focusing on pantoprazole's use as a proton pump inhibitor for conditions like GERD and Zollinger-Ellison syndrome. It details the direct compression method for tablet manufacturing, including various excipients and their functions, as well as the importance of enteric coating to protect the drug from the stomach's acidity. The evaluation process for the formulated tablets includes testing for dissolution, content uniformity, weight variation, hardness, friability, and disintegration times.

1. OBJECT- FORMULATION AND EVALUATION OF PANTAPRAZOLE TABLET
SUBMITTED BY:
AMIT PRATAP SINGH

2. TO FORMULATE, EVALUATE,AND DEVELOP
ENTERIC COATED PENTOPRAZOLETABLET.
. Introduction
 Pantoprazole is a first-generation proton pump inhibitor (PPI) used for the management
of gastroesophageal reflux disease (GERD), for gastric protection to prevent recurrence of
stomach ulcers or gastric damage from chronic use of NSAIDs, and for the treatment of
pathological hypersecretory conditions including Zollinger-Ellison (ZE) Syndrome.

3. CONT…..
• The key action mechanism of the PPIs is inhibition of H+/K+-adenosine
triphosphate, an enzyme present in the gastric parietal cells.These drugs are
metabolized in the parietal cells to active sulfonamide metabolites that inactivate the
sulfhydryl group of the proton pump, thus reducing the hydrogen ion secretion.
• Due to the pH sensitivity of Pantoprazole Sodium, effective drug delivery is
problematic. Most of the PPIs are formulated in an enteric-coated solid dosage form
(either a delayed-release capsule or tablet) or as an intravenous solution.

4. CONT….
• Pantoprazole is also used to treat Zollinger-Ellison syndrome and other
conditions involving excess stomach acid.
• Long-term treatment with pantoprazole may also make it harder for your
body to absorb vitamin B-12, resulting in a deficiency of this vitamin.
• Common side effects include headaches, constipation or diarrhoea, wind,
stomach pain, feeling or being sick.

5. DIRECT COMPRESSION METHOD
• The term direct compression (or direct compaction) is used to define the
process by which tablets are compressed directly from powdered active
drug substance and suitable excipients into a firm compact without
employing the process of granulation.
• No pretreatment of the powder blend by wet or dry granulation procedure
is required. Direct compression is a dry process where in the powdered
material (tablet formulation) is compressed directly into the tablets without
the physical nature of the former being modified.

6. TECHNIQUES IN DIRECT COMPRESSION
(1)Direct compression technique using induced die feeders
(2)Direct compression technique using dry binders and
(3)Direct compression technique using direct compression excipients

7. EXCIPIENTS USED IN THE MANUFACTURE OF
TABLETS BY DIRECT COMPRESSION METHOD
a. Diluents/fillers: Examples of diluents used in direct compression
technology include Spray-dried lactose,Dicalcium phosphate (e.g.
Encompress grades),Mannitol,Sorbitol,Microcrystalline cellulose (e.g.
Avicel pH-102)
b. Compression aid:Examples of commonly used compression aids
include Microcrystalline cellulose (e.g. Avicel pH-102) and directly
compressible starch.

8. CONT……
c. Disintegrants:Examples of excipients that are commonly used as disintegrants
for direct compression technology include: Pregelatinised starch (e.g. Starch
1500),Sodium starch glycolate (e.g. Explotab, Primojel),Croscarmellose sodium
(e.g. Ac-Di-Sol, Explocel),Crospovidone (e.g. Polyplasdone XL, Polyplasdone XL-
10, Kollidon CL, Kollidon CL-M).
d. Lubricants and glidants:The types of lubricants and glidants used in the
manufacture of tablets by direct compression method are similar to those used in
other tablet manufacture methods and include:Lubricants (e.g., magnesium stearate,
stearic acid, sodium stearyl fumarate) Glidants (e.g., talc, colloidal silicon dioxide).

9. ADVANTAGES OF DIRECT COMPRESSION
• The prime advantage of compression over wet granulation is economic
due to fewer unit operations.
• Requirement of equipment, power consumption,time and labor leading
to reduced production cost of tablets.
• It is more suitable for moisture and heat sensitive APIs because it
eliminates wetting and drying steps and increases the stability of active
ingredients by reducing detrimental effects.

10. CONT…….
• Materials are "in process" for a shorter period of time, therefore less chance for
contamination or cross contamination, and making it easier to meet the requirement
of current good manufacturing practices.
• Chance of microbial growth is minimum due to absence of water.
• Tablets prepared by direct compression disintegrate into API particles instead of
granules that directly come into contact with dissolution fluid and exhibits
comparatively faster dissolution, whereas disintegration or dissolution is the rate-
limiting step in absorption in the case of tablets of poorly soluble API prepared by
wet granulation.

11. ENTERIC COATING
• An enteric coating is a polymer barrier applied to oral medication that
prevents its dissolution or disintegration in the gastric environment.
• The word “enteric” indicates small intestine; therefore enteric coatings
prevent release of medication before it reaches the small intestine.

12. • The enteric coated polymers remain unionise at low pH, and therefore remain insoluble.
• But as the pH increases in the GIT, the acidic functional groups are capable of ionisation, and
the polymer swells or becomes soluble in the intestinal fluid.
• Materials used for enteric coatings include CAP, CAT, PVAP and HPMCP, fatty acids, waxes,
shellac, plastics and plant fibers.
CONT......

13. REASON FOR ENTERIC COATING
• Protection of active pharmaceutical ingredients, from the acidic
environment of the stomach.
• To prevent gastric distress or nausea from a drug due to irritation.
• For the delivery of drugs that are optimally absorbed in the small
intestine to their primary absorption site in their most concentrated form.
• Required for minimizing first pass metabolism of drugs.

14. FORMULA TABLE
ORIGINAL FORMULA MODIFIED FORMULA
PANTOPRAZOLE SODIUM PANTOPRAZOLE SODIUM
MCC DIRECTLY COMPRESSIBLE STARCH
CROSS CARMELOSE SODIUM SODIUM STARCH GLYCOLATE
MANITOL SORBITOL
DICALCIUM PHOSPHATE SPRAY DRIED LACTOSE
TALC AEROSIL 200
MAGNESIUM STERATE STEARIC ACID

15. ENTERIC COATING(FORMULA TABLE)
MATERIAL USES
EUDRAGIT L100/CELLULOSE ACETATE
PTHALATE
ENTERIC POLYMER
PEG PLASTICIZER
ACETONE SOLVENT
ISOPROPYL ACETONE SOLVENT

16. PROCEDURE
• Core tablet making:
• Premilling of formulation ingredients (active drug substance and excipients).
• Mixing of active drug substance with the powdered excipients (including the
lubricant).
• Compression of the mixed powders into tablets.

17. CONT…..
• Preparation of enteric coating material
• The enteric coating solution was prepared by simple solution method. It was prepared by 6%
w/w and 8% W/W of Eudragit L100 (E1 and E2) or cellulose acetate phthalate (C1 and C2) as
an enteric polymer, PEG 1.5% w/w as plasticizer and acetone and isopropyl acetone was used
as solvent. Diethyl phthalate was added and made up the volume with rest of the solvent
mixture,this mixture was constantly stirred for 1h with paddle mechanical stirrer at the rate of
1000 rpm and the stirred coating solution was again filtered through muslin cloth, a coating
solution was obtained.

18. CONT….
• Enteric coating of pantoprazole sodium compressed tablets by dipping method: The
compressed tablets were coated with enteric coating polymer (Eudragit L100 or cellulose
acetate phthalate) solution by dipping method.
• Desired tablet coating continued the dipping and weight gain was achieved.
• The coated tablets were studied for its weight variation, thickness, uniformity of drug
content and in vitro dissolution study.

19. EVALUATION
• Dissolution- it may be def9nd as the amount of drug substance that goes into solution per unit
time under standardized condition of liquid/ solid interface, temp, and solvent compounds.
• Different apparatus for dissolution-according to USP
1.Basket type
2.Paddle type
• Content uniformity-10 tablets are taken at random, there content of active ingredient is
determined(uv spectrometer) an dthe average value is calculated. (limit-if 2 or 3 tablets are
outside limit 85 to 115% of the average value then none is outside the limit 75 to 125%.

20. CONT……
• Weight variation-weight 20 tablets selected at random and determine the average weight.
According to ip limits:
• Hardness- ideal hardness is 5 kg. tested by Monsanto tester, Pfizer tester.
Average weight Max. % difference allowed
80 mg or less +-10%
80-250 mg +-7.5%
More than 250 mg +-5%

21. CONT….
• Friability- The friability test is official in USP but not in IP and BP.
-apparatus – Roche friabilator
-pre weighted tablets sample placed in friabilator. Operated for 100 revolutions (at 25 rpm for 4 min.)
-dropping tablet distance 6 inch.
-limit-0.5 to 1% loss of weight of each tablet are generally acceptable.
• Disintegration-The Usp device to test disintegration uses 6 glass tubes that are 3 inch long, open at
the top and 10 mesh screen at the bottom end.
-Disintegration time for enteric coated tablets:
0.1 n hcl- not less tham 120 min
Phosphate buffer,6.8 ph-upto 60 min

22. RESULT
• The pantoprazole enteric coated tablet was formulate,evaluate and
developed.

23. REFERENCES
• Chakraborty S, Sarkar S, Debnath SK. Formulation development and evaluation of
pantoprazole enteric coated tablets. International Journal of ChemTech Research. 2009
Sep;1(3):663-6.
• Iqubal MK, Singh PK, Shuaib M, Iqubal A, Singh M. Recent advances in direct compression
technique for pharmaceutical tablet formulation. International journal of pharmaceutical
research and development. 2014;6(1):49-57.