FORMULATION AND EVALUATION OF DISPERSIBLE TABLETS WITH
`PREGELATINIZED STARCH
`
`K.P .R. Chowdary and N. Rama Rao
`
`(Received 27 January 1998)
`
`INTRODUCTION
`
`Dispersible tablets of norfloxacin, paracetamol
`and piroxicam formulated with pregelatinized starch
`(PGS) fulfilled the official (1.P.) requirements of
`dispersible tablets and gave fast and rapid dissolution
`of the contained medicament when compared to
`conventional tablets.
`
`Pregelatinized starch (PGS) is a modified starch
`that has been modified chemically or mechanically
`processed to rupture all on part of the starch
`granules. It is used in oral capsule and tablet
`formulations as a diluent1 an~ disintegrant2. Though
`many modified starches have been studied3·7 widely
`for their pharmaceutical applications, PGS has not
`been investigated throughly. PGS was reported to
`enhance the dissolution rate of salicylic acid8 and
`acetaminophen9 from tablet formulations. We have
`been working on the pharmaceutical applications of
`PGS. The objective of the present study is to evaluate
`PGS for its application in the formulation of dispersible
`tablets. Dispersible tablets of norfloxacin (NF),
`paracetamol (PA) and piroxicam (PY) were
`formulated employing PGS and were evaluated.
`The results are reported here.
`
`METHODS
`
`Materials: Norfloxacin, U.S.P., Paracetamol, I.P.,
`Pirxociam, U.S.P., Pregelatinized starch (prepared
`
`from potato starch in the laboratory by a known
`method10), polyvinyl pyrrolidone (Mel.Wt. 40,000),
`Lactose, I.P., Talc, I.P. and Magnesium stearate, I.P.
`were used.
`
`Norbid (Norfloxacin 100mg, Cipla), Norflox
`(Norfloxacin 200mg, Cipla), Tyfy (Paracetamol
`125mg, Legend), Metacin (Paracetamol 500mg,
`Themis), Pirox OT (Piroxicam 200mg, Cipla) and
`Suganril (Piroxicam 20mg, SG Pharma) were
`procured from local market and were used.
`
`Preparation of dispersible tablets
`
`Dispersible tablets of (i) NF (100mg) (ii) PA
`{125mg) and (iii) PY {20mg) were prepared as per
`formulae given in Table-1 by conventional wet
`granulation method. Tablet granulations were
`compressed into tablets to a hardness of 5-6Kg/
`Sq.cm on "Cadmach" single punch tablet machine.
`
`Disintegration times were determined in
`"Thermonic" tablet Disintegration Test Machine,
`U.S.P. standard using distilled water as the fluid.
`Hardness of the tablets was tested using "Monsanto"
`Hardness Tester. Friability of the tablets was
`determined in Roche .Friabilator. All the tablets were
`tested for uniformity of dispersion as per I.P. test11.
`Known spectrophotometric methods were used for
`the estimation of NF12 , PA13 and py14.
`
`*For correspondence
`Siddhartha College of Pharmaceutical Sciences
`Vijayawada-10, A.P.
`
`Dissolution rate study
`
`This dissolution rate ·of NF, PA and PY from
`
`INDIAN DRUGS 35(6) JUNE 1998
`
`368
`
`This material was Hipied
`at the NLM and maybe
`5'ubject USCop1right Laws
`
`Par Pharm., Inc.
`Exhibit 1011
`Page 001
`
`

`

`dispersible tablets prepared as well as commercial
`dispersible and conventional tablets was studied
`using USP XXI Dissolution Rate Test Apparatus
`employing paddle stirrer. Acetate buffer of pH 4.0
`(750 ml), phosphate buffer of pH 7.8 (900 ml) and
`0.1 N hydrochloric acid (900 ml) were used as
`dissolution fluids for NF, PA and PY respectively. In
`each test one tablet, a speed of 100 rpm and a
`temparature of 37° ± 1 °C were employed. A 5 ml
`aliquot of dissolution medium was withdrawn through
`a filter at different time intervals, suitably diluted and
`assayed spectrophotometrically at 278 nm for NF,
`249 nm for PA and 333 nm tor PY. Dissolution
`efficiency (D.E.) values were calculated from the
`dissolution date as suggested by Khan 15
`
`•
`
`RESULTS AND DISCUSSION
`
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`
`Pregelatinized starch, prepared from potato
`starch by a known method, was used in the present
`study. The PGS prepared fulfilled the official (XXIII)
`identification tests and test for absence of oxidising
`substances. The PGS prepared was insoluble and
`easily dispersible in purified water. The pH of a 10%
`WN slurry in water was 7.2.
`
`All the tablets were found to contain the
`medicament within 100 ± 5 percent of the labelled
`claim. Hardness of the tablets was found to be within
`the range of 5-6 Kg/Sq.cm and was satisfactory.
`Friability of all the tablets was less than 1 %. All the
`dispersible tablets disintegrated within 3 minutes
`fulfilling the official (1.P.) requirement for dispersible
`tablets. In the test for uniformity of dispersion, all
`dispersible tablets containing PGS at 10% and above
`concentration fulfilled the official requirement. The
`dispersion produced in water passed through mesh
`No. 22. Whereas conventional tablets did not pass
`this test and about 15-25 percent of the total mass
`was retained on mesh No. 22.
`
`With all the three medicaments dispersible tablets
`
`369
`
`INDIAN DRUGS 35(6) JUNE 1998
`
`Th is mate ria I was rnefied
`at the NLM and may bE
`Subject US Cop','right laws
`
`Par Pharm., Inc.
`Exhibit 1011
`Page 002
`
`

`

`Table 2 : Disintegration and dissolution characteristics of various tablets
`
`Tablet
`
`D.T.
`(min)
`
`Hixson-Crowell's
`Dissolution Rate
`(mg113 min"1) (±SD)
`
`Dissolution
`efficiency
`(%)
`
`C
`
`DF1
`
`DF2
`
`DC
`
`C
`
`DF1
`
`DF2
`
`DC
`
`C
`
`DF1
`
`DF2
`
`DC
`
`4.0
`
`1.0
`
`1.5
`
`1.0
`
`9.5
`
`1.5
`
`1.5
`
`2.5
`
`11.0
`
`1.5
`
`1.5
`
`1.5
`
`Norfloxacin
`
`0.034 ± 0.015
`
`0.115 ± 0.018
`
`0.140 ± 0.009
`
`0.144 ± 0.008
`
`Paracetamol
`
`0.035 ± 0.019
`
`0.077±0.014
`
`0.085 ± 0.023
`
`0.058 ± 0.007
`
`Piroxicam
`
`0.036 ± 0.098
`
`0.077 ± 0.009
`
`0.085 ± 0.006
`
`0.059 ± 0.012
`
`65.33
`
`88.00
`
`90.22
`
`90.66
`
`80.26
`
`90.80
`
`92.10
`
`90.50
`
`36.68
`
`79.83
`
`84.26
`
`75.67
`
`C : Conventional; DF1: Dispersible formulated (PGS 10%};
`DF2: Dispersible formulated (PGS 20%}; DC : Dispersible commercial.
`
`both prepared with PGS and commercial gave very
`fast and rapid dissolution of the contained
`medicament when compared to the corresponding
`conventional tablets (Table-2). Dissolution efficiency
`was also high in the case of disper&ible tablets.
`Dissolution of medicament from these tablets obeyed
`Hixson-Crowell's cube root equation.
`
`ACKNOWLEDGEMENTS
`
`The authors are grateful to Siddhartha Academy
`of General and Technical Education, Vijayawada for
`providing necessary facilities.
`
`REFERENCES
`
`Thus dispersible tablets of NF, PA and PY could
`be formulated employing pregelatinized starch. A
`concentration of 10-20% of PGS in the formula is
`optimum for formulation of dispersible tablets.
`
`1. Small LE, Augsburger LL. ,Drug Dev. Ind. Pharm., 1978,
`4,345.
`
`2. Rudnic EM, Rhodes CT, Welch S, Bernardo P., Drug
`Dev. Ind. Pharm., 1982, 8, 87.
`
`INDIAN DRUGS 35(6) JUNE 1998
`
`370
`
`This material was coP"ied
`at the NLM and may bE
`5'ubject USCoP"yright Laws
`
`Par Pharm., Inc.
`Exhibit 1011
`Page 003
`
`

`

`3. Schmidt, P.C., Broegmann, 8., Acta Pharm. Technol.,
`1988, 34, 22.
`
`4. Cohen, J. and Lach, J.L, J. Pharm. Sci., 1963, 52, 132.
`
`5. Tarimci, N. and Celebi, N., Pharmazie., 1988,
`43, 323.
`
`6. Sekulovic, D. and Zajic, L., Pharmazie., 1987, 42,
`556.
`
`1 o. Handbook of Pharmaceutical Excipients., 2nd Ed.,
`Edited by Ainley Wade and Paul J Weller, The
`Pharmaceutical Press, London, 1994, p 491-493.
`
`11.
`
`Indian Pharmacopoeia, 1996, Ministry of Health and
`Family Welfare, Govt. of India, Delhi, 1996, p. 736.
`
`12. The United States Pharmacopoeia, 23rd Ed., U.S.
`Pharmacopoeia! convention, Inc., Rockville, Md., 1995,
`p 1104.
`
`7. Uekama, K., Hirashima, N., Hboriuchi, Y., Hirayama, F.,
`Ueno., M., J.Pharm. Sci., 1987, 76, 660.
`
`13.
`
`Indian Pharmacopoeia, 1996, Ministry of Health and
`Family Welfare, Govt. of India, Delhi, 1996, p. 556.
`
`8. Underwood TW, Cad Wallader DE., J. Pharm. Sci.,
`1972, 62, 239.
`
`9. Symecko C.W., Rhodes, C.T., Drug Dev. Ind. Pharm.,
`1997, 23, 229.
`
`14. The United States Pharmacopoeia, 23rd Ed., U.S.
`Pharmacopoeia! convention, Inc., Rockville, Md., 1995,
`p. 1235.
`
`15. Khan, K.A., J. Pharm. Pharmacol., 1975, 27, 48.
`
`MANAGING DIABETES AFTER MYOCARDIAL INFARCTION
`
`This major randomised control trial confirmed and
`extended observations from smaller studies of the
`relation between diabetic control and the development
`of small vessel disease and neuropathy. However, no
`previous studies have argued convincingly for a relation
`between diabetic control and macrovascular disease,
`which remains the major cause of mortality in diabetic
`patients and makes a substantial contribution to
`morbidity.
`
`Undoubtedly, insulin and insulin treatment of
`diabetes should become part of a more aggressive
`approach to managing diabetic patients after myocardial
`infarction. Attempts to improve management in this
`area have been bedeviled by an unjustified reluctance
`to translate evidence into practice or, perhaps with
`somewhat greater justification, to extrapolate from the
`
`non-diabetic situation. Thus, thrombolysis, probably
`the single most important measure and one that has
`been shown to almost halve mortality in hospital after
`infarction, is withheld because of vague fears of its
`impact on diabetic retinopathy; and other agents that
`have been shown to be of benefit in diabetic patients,
`such asp blockers, are not used because they alter the
`lipid profile or mask hypoglycaemic symptoms, minor
`considerations in both effect and importance when set
`against mortality. Angiotension converting enzyme
`inhibitors, aspirin, and cholesterol lowering drugs might
`also form part of this more aggressive package of care.
`Hopefully, the findings of this present study do not
`flounder on a reluctance on the part of either patients
`of doctors to introduce insulin.
`
`Courtesy: M. Nattrass, BMJ, May 1997; 314: 1497.
`
`371
`
`INDIAN DRUGS 35(6) JUNE 1998
`
`This material was copied
`at the N LM a rid may be
`5'ubject US Copyright Laws
`
`Par Pharm., Inc.
`Exhibit 1011
`Page 004
`
`