Development, Standardizationand Evaluation of Sennosides a & B Capsule

DEVELOPMENT, STANDARDIZATIONAND EVALUATION OF SENNOSIDES A & B CAPSULE

M. Pharm Dissertation Protocol Submitted to

Rajiv Gandhi University of Health Sciences, Karnataka

Bangalore – 560041

MR. RATAN BIRADAR ,B. Pharm.

Under the Guidance of

Dr. R. A. ShastriM.Pharm,Ph.D,

Asst.Professor

Post Graduate Department of Pharmacognosy,

SET’S College of Pharmacy,

S.R.Nagar, Dharwad,

Karnataka–580 002.

2013-2014

[

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

KARNATAKA, BANGALORE.

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1 / NAME OF THE CANDIDATE AND
ADDRESS OF THE CANDIDATE / Mr. Ratan Biradar
Post Graduate Department of Pharmacognosy,
SET’s College of Pharmacy,
S.R.Nagar, Dharwad,
Karnataka – 580 002.
E-mail ID:
2 / NAME OF THE INSTITUTION / SET’S COLLEGE OF PHARMACY
S.R.Nagar, Dharwad,
Karnataka – 580002.
3 / COURSE OF STUDY
AND SUBJECT / MASTER OF PHARMACY IN PHARMACOGNOSY
4 / DATE OF THE ADMISSION / July-2013
5 /

TITLE OF THE TOPIC

DEVELOPMENT, STANDARDIZATION AND EVALUATION OF SENNOSIDESA AND B CAPSULE
6 / BRIEF RESUME OF THE INTENDED WORK
6.1 / Need for study
A very famous Sholka in Sanskrit

This means “There is nothing in this universe, which is non-medicinal, which cannot be made use of for many purpose and by many modes”. In practice however we call a plant medicinal when it is actually in use in some system of medicine.
Ayurveda emphasis the relationship between man and plants throughout the development of human culture. The use of herbal medicine due to toxicity and side effects of allopathic medicines, has led to sudden increase in the number of herbal drug manufactures.1
World Health Organization (WHO) has defined herbal medicines as finished labeled medicinal product that contain active ingredients, aerial or underground parts of the plant or other plant material or combinations.2
Herbal medicines as the major remedy in traditional system of medicine have been used in medical practices since antiquity. The practices continue today because of its biomedical benefits as well as place in cultural beliefs in many parts of world and have made a great contribution towards maintaining human health.3
Cassia angustifolia Valh. (Leguminoseae) is a well-known herbal laxative drug and is included in many pharmacopoeias. The active constituents sennoside A and B, mainly act upon the large intestine and are therefore, especially suitable in habitual constipation. The glycosides are absorbed from the intestinal tract and the active anthraquinone are excreted into the colon, where they stimulate and increase the peristaltic movements of the colon by local action. This results in decreased absorption of water and thereby a bulky and softer fecal mass is produced. This suggests their action in lower bowl and no effect in stomach and small intestine. By targeting we can ensure that entire quantity of sennoside is made available to colon thereby obviating any possible loss during passage through systemic circulation. Hence, in the present investigation, drug is targeted directly to the colon in order to produce optimal result.
6.2 / Review of Literature
Senna known as Tinnevelly senna, family Leguminoseae,4 mainly act upon the large intestine. The glycosides are absorbed from the intestinal tract and the anthraquinone are excreted into the colon, where they stimulate and increase the peristalic movements of the colon by local action. This results in decreased absorption of water and thereby a bulky and softer fecal mass is produced. This suggests their action in intestine and no effect in stomach. 5-7
Senna is a well known drug, used in the Ayurvedic and Allopathic systems of medicine for treatment of constipation. The laxative action of senna and its formulations is due to the presence of sennosides A and B.
By targeting the sennoside to intestine with the help of enteric coating, we can ensure that entire quantity of drug is made available to intestine thereby averting any possible loss during passage through the stomach. 8
Certain solid dosage foms are used to evaluate the therapeutic effect on targeted site of animals.
Solid dosage forms (SDF) are the drug delivery devices formulated as both single and bulk dose forms suitable for oral administration. It mainly comprises of tablets, capsules, cachets, pills, powders and granule forms.
Capsules are solid unit dosage form of medicament in which the drug is enclosed in a hard or soft container or shell made of suitable form of gelatin.
Various reports mentioning; the concepts of sennosides A & B & their Pharmacological actions are reported; few of them are mentioned below.
The leaves containing sennosides are efficient sources of health teas 9and are considered as astringent, cathartic, depurative, anthelmintic, cholagogue, expectorant and febrifuge, useful for leprosy, leukoderma, jaundice, typhoid fever and tumors10.Antibacterial11,Invitro evaluation of sennoside using pectin for colon drug delivery were reported12,In- vitro studies on guargum based formulation for the colon targeted delivery of sennosides were reported13. In the present investigation, granules containing standardized extracts of sennoside A and B, gum caraya and other excipents will be prepared as per the standard methods and will be formulated in capsule dosage forms , developed and evaluated for it’s in-vitro and in-vivo parameters.
6.3 / Objectives of the study
The objective of the proposal here is the Development, Standardization and Evaluation of Sennosides A & B Capsule:

Developmentof Sennoside A & B Capsule,
Standardization of Sennoside A & B Capsule,
Evaluation of Sennoside A & B Capsule,
Study the Stability of Preparations,
Publish the data derived from this work.

7 / MATERIALS AND METHODS
7.1 / Sources of Data
J-Gate@Helinet,
Pub med,
Highwire Press,
Science direct,
World Health Organization (WHO),
Wikipedia,
Library of SET’s College of Pharmacy,
Library of SDPC & SDPARC.
7.2 / Method of Collection of Data
The sources of data are from the laboratory experiments, which involve development, standardization and therapeutic evaluation of Sennoside A & B Capsule.
7.3 / Development of Sennoside A & B Capsule
Development of the formulation shall be done based upon the kind of extracts/herbs that will be base on the preformulation study, selecting hard or soft gelatin and formulation of blend will be based on selection of bulking agent/diluent, disintegrating agent, glidant and lubricant.
7.4 / Standardization of Sennoside A & B Capsule
Standardization of the formulation shall be done based upon the kind of extracts/herbs that will be finalized in the preparation. Markers (respective) shall be obtained & correlated with the concentration of extracts & formulations.
7.5 / Evaluation of Sennoside A & B Capsule14

In vitro Evaluation using Dissolution Apparatus

Medium: water; 900 mL.
USP Apparatus 1: 100 rpm.
Time: 120 minutes.
Procedure— Determine the amount of sennosides dissolved, as per standardization method.
Tolerances— Not less than 75% (Q) of the labeled amount of sennosides is dissolved in 120 minutes.
Estimation of sennoside content by HPLC method

In-vivo Evaluation 15-17

For measurement of large intestinal transit time
female Wistar rats weighing approximately 200 g are anesthetized with ether. A PVC catheter is implanted into the caecum with the distal end fixed on the animal’s neck. The animals are allowed to recover and are placed individually in a wire meshed cage to enable the feces to fall through onto blotting paper. Carmine red (10 mg in 0.4 ml distilled water per animal)
is injected through the catheter immediately after administration of the test substance. The time until appearance of the first colored feces is registered.
For measurement of fluid absorption in the colon
female Wistar rats weighing approximately 200 g are anesthetized with 50 mg/kg pentobarbitone sodium. The colon is ligated and cannulated distal to the caecocolic junction (PE-tube, i.d. 1 mm) and, after a thorough rinse with 50 ml physiological saline to remove all contents, a second cannula (silicone, i.d. 3 mm) is inserted proximal to the rectum for fluid outflow. Four and 6 h after oral administration of the test compoundsan open perfusion with an electrolyte solution (NaCl 6.72 g/l, KCl 0.37 g/l, NaHCO3 2.1 g/l, polyethylene glycol (PEG, mol wt 4 000) 2.0 g/l, [14C]PEG 5 μCi/l; pH 6.5, osmolality 275 milliosmol/kg) is started at a rate of 12 ml/h for two consecutive 2 h periods. [14C]PEG activity is measured by liquid scintillation counting, Na+ and K+ by flame photometry, Cl– by coulometrictitration, osmolality by freezing point depression and mucus as protein-bound total hexoses by the orcinolsulphuric acid method. Net H2O, Na+, K+ and Cl– transport are calculated and expressed as ml or μmol/h andper 10 cm colon length.
EVALUATION
All values are expressed as mean ± standard deviation. Statistical significance is assessed with Student’s t-test.
7.6 / Study the Stability of Preparations
As per the ICH guidelines.
7.7 / Does the study require any investigation or interventions to be Conducted on patients or other humans or animals?If so please describe briefly.
The above study requires investigations to be done onwistar ratsto determinethe laxative effect of sennoside A and B. The study is planned in accordance with the procedure reported in the literature.
7.8 / Has ethical clearance been obtained from your institution in case of 7.7?
The copy of the ethical clearance certificate is attached.
8 / REFERENCES
1. Shah SA, Ravishankara MN, Nirmal A, Shishoo CJ, Rathod IS, Suhagia BN, Estimationof individual sennosides in plant materials and marketed formulations by an HPTLCmethod, Journal of Pharmacy and Pharmacology, 2000; 52(4), 445-449.
2. United States Pharmacopoeia 27, U.S pharmacopoeia convention, Inc, Rockville,MD, Webcom limited, Toronto, 2004, 1686-1688.
3. The international pharmacopoeia, Quality specifications Geneva world health organization,IIIrd edn, Vol 3, 1988, 284-289.
4. British Pharmacopoeia, Vol. 3, Her Majesty’s Stationary Office, London, 2004, 1738-1739.
5. Momin M, Pundarikakshudu K, Design, development and in vitro evaluation ofsennosides tablets containing pectin HPMC for colonic drug delivery, Indian Journalof Pharmaceutical Sciences, 2007; 67(4): 394-401.
6. Fairbairn JW, The active constituents of the vegetable purgatives containing anthracenederivatives, Journal of Pharmacy and Pharmacology, 1994; 1: 683-686.
7. Franz G, The senna drug and its chemistry, Pharmacology, 1993; 47: 2-6.
8. Momin M, Pundarikakshudu K, In vitro studies on guar gum based formulation forthe colon targeted delivery of sennosides, Journal of Pharmacy and PharmaceuticalSciences, 2004; 7(3): 325-331.
9. Kojima T, Kishi M, Sekita S and Satake M. 2001. Origin of sennosides in health teas including Malva leaves. Shokuhin Eiseigaku Zasshi , 2013; 42: 202–205.
10.Warier PS. 1994. Indian Medicinal Plants, New Delhi, Orient Longman Publication , 2: 31.
11. Zakaria Bameri, Negar Amini-Boroujeni, Saeide Saeidi, Saphora Bazi.Antibacterial activity of Cassia angustifolia Extract Against Some Human Pathogenic Bacteria. J Nov . Appl Sci., 2013; 2 (11): 584-586.
12. Munira Momin, K Pundarikakshudu.Design, development and in vitro evaluation of sennosides tablets containing pectin HPMC for colonic drug delivery.Indian Journal of Pharmaceutical science,2007; 69(3):394-401.
13.Munira Momin, K Pundarikakshudu.In-vitro evaluation on guargum based formulation for the colon targeted delivery of sennosides.J pharm pharmaceut sci 2004;7(3):325-331.
14. Bleasel MD, Aldous S. In vitro evaluation of sun protection factors of sunscreen agents using a novel UV Spectrophotometric technique. International Journal of Cosmetic Science 2008; 30: 259-270.
15.Leng-Peschlow E, Acceleration of large intestine transit time in rats by sennosides and related compounds. J Pharm Pharmacol 1986; 38: 369–373.
16.Leng-Peschlow E, Dual effect of orally administered sennosides on large intestine transit and fluid absorption in the rat. J Pharm Pharmacol 1986; 38: 606–610.
17.Ogunti EO, Elujoba AA, Laxative activity of Cassia alata. Fitoterapia 1993; 64: 437–439.

9 SIGNATURE OF THE CANDIDATE

/ (Mr.Ratan Biradar)
10 / REMARKS OF THE GUIDE / The above mentioned information and literature has been extensively investigated, verified and was found to be correct. The present study will be carried out under my supervision and guidance.
11 / NAME AND DESIGNATION
OF
GUIDE

SIGNATURE

/ DR. R. A. SHASTRI,M. Pharm. Ph.D.
Asst.Professor,
Post Graduate Department of Pharmacognosy,
SET’s College of Pharmacy, S.R.Nagar,
Dharwad. Karnataka – 580 002.
Mobile No.: +91-9980732064
E-mail:

12 NAME AND DESIGNATION

OF

CO – GUIDE

SIGNATURE / -
13 / NAME AND DESIGNATION
OF
HOD
SIGNATURE / Dr. P. V. HABBU,M. Pharm. Ph.D.
Professor & HOD
Post Graduate Department of Pharmacognosy,
SET’s College of Pharmacy, S.R.Nagar,
Dharwad. Karnataka – 580 002.
Mobile No.: +91 – 9448224894
E-mail:

14 REMARKS OF PRINCIPAL

/ The above mentioned information is correct and I recommend the same for approval.
15 / NAME OF THE PRINCIPAL
SIGNATURE / Dr. V. H. KULKARNI,M. Pharm. Ph.D.
Principal, SET’s College of Pharmacy,
S.R.Nagar, Dharwad. Karnataka – 580002.
Mobile No.: +91 – 9448357804
E-mail: