Formulation and Evaluation of Coated Ramipril Tabletsby Direct Compression Method

FORMULATION AND EVALUATION OF COATED RAMIPRIL TABLETSBY DIRECT COMPRESSION METHOD

SYNOPSIS FOR

M.PHARM DISSERTATION

SUBMITTED TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA.

SUBMITTED BY

SRINIVAS.MOTURI

M.PHARM PART 1st YEAR

DEPARTMENT OF PHARMACEUTICS

UNDER THE GUIDANCE OF

Mrs. SURINDER KAUR

Assistant Professor

THE OXFORD COLLEGE OF PHARMACY

BANGALORE-68.

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA.

ANNEXURE – II

Proforma for Registration of Subject for Dissertation

1. / Name of the candidate and address / Mr. SRINIVAS.MOTURI
DEPARTMENT OF PHARMACEUTICS,
THE OXFORD COLLEGE OF PHARMACY,
No.6/9, 1ST CROSS, BEGUR ROAD,
HONGASANDRA, BENGALURU –560 068
KARNATAKA.
PERMANENT ADDRESS
SH.No: 13, SHOPPING COMPLEX,
8 INCLINE COLONY, GODAVARIKHANI ,
RAMAGUNDAM (Division)
KARIMNAGAR(Dist),
ANDHRA PRADHESH-505211.
2. / Name of the institution / THE OXFORD COLLEGE OF PHARMACY,
No.6/9, 1ST CROSS, BEGUR ROAD,
HONGASANDRA, BENGALURU –560 068
KARNATAKA.
3. / Course of study and subject / Master of Pharmacy in Pharmaceutics
4. / Date of admission to course / 09/11/ 2010
5. / Title of the topic:
“FORMULATION AND EVALUATION OF COATED RAMIPRIL TABLETS
BY DIRECT COMPRESSION METHOD”
6.
7.
8. / Brief Resume of Intended Work:
6.1: Need for the Study:
Hypertension1 is defined as either a sustained systolic blood pressure (SBP) of greater than 140 mm Hg or a sustained diastolic blood pressure (DBP) of greater than 90 mm Hg. Hypertension results from increased peripheral vascular smooth muscle tone, which leads to increased arteriolar resistance and reduced capacitance of the venous system.
Hypertension is the principal cause2 of stroke and it is a major risk factor for coronary artery disease and its attendant complications myocardial infarction, sudden cardiac death, it is a major contributor to cardiac failure, renal insufficiency, and dissecting aneurysm of the aorta. So it is needed to treat Hypertension, Antihypertensives are used for this purpose.
Antihypertensives are divided into various classes3 like Diuretics, ACE inhibitors, Angiotensin blockers, Calcium channel blockers, Vasodilators, Central sympatholytics, and various Adrenergic blockers.
Amongst these, the ACE inhibitors are the first choice of drugs in all grades of essential as well as renovascular Hypertension.4
For the administration of these Antihypertensive agents, oral solid dosage form is most commonly preferred.
 Oral administration of drugs has been the most common and preferred route for delivery of most therapeutic agents5. The popularity of the oral route is attributed to the patient acceptance, ease of administration, accurate dosing, cost effective manufacturing method, least sterility constraints, flexible design of dosage forms and generally improved shelf-life of the product.
Amongst these solid oral dosage forms, tablets are the most convenient dosage forms and hence widely used in the chemotherapeutic field and it comprises of only a few working steps6. The material used for the production of tablet should be in physical form that flows smoothly, compressible and physically stable so as to achieve rapid production capability of tablet formulation.
The manufacture of tablets is carried out by techniques7 which are:

1. Direct compression
2. Dry granulation
3. Wet granulation

Amongst the above techniques used to prepare tablets, direct
compression is the most advanced technology8. It involves only blending and
compression. Thus offering advantage particularly in terms of speedy
production. Because it requires fewer unit operations, less machinery, reduced
number of personnel and considerably less processing time along with increased
product stability.
Definition: The term “Direct compression8” is defined as the process by which tablets are compressed directly from powder mixture of API and suitable excipients. No pre-treatment of the powder blend by wet or dry granulation procedure is required.
The events that motivate the industry people to use direct compression technique8

1. Commercial availability of the directly compressible excipients possessing both good compressibility and good flowability.
2. For example, Spray dried lactose, Anhydrous lactose, Starch-1500, microcrystalline cellulose, Di-PacÒ, Sorbitol.
3. Major advances in tablet compression machinery:

i)Improved positive die feeding,
ii)Precompression of powder blend.

Merits:

i)Direct compression is more efficient and economical process as compared to other processes, because it involves only dry blending and compaction of API and necessary excipients.
ii)The most important advantage of direct compression is, it is economical, reduced processing time, reduced labour cost, fewer manufacturing steps, utility of minimal equipments, less process validation and reduced consumption of power.
iii)Elimination of heat and moisture, increases not only the stability but also the suitability of the process for thermolabile and moisture sensitive API’s.
iv)Particle size uniformity.
v)Prime particle dissolution. In case of directly compressed tablets after
disintegration, each primary drug particle is liberated. While in the case of
tablets prepared by compression of granules, small drug particles with a larger
surface area adhere together into larger agglomerates thus, decreasing the
surface area available for dissolution.
vi)The chances of batch-to-batch variation are negligible, because, the unit operations required for manufacturing processes is fewer.
vii)Chemical stability problems for API and excipient would be avoided.
viii)Provides stability against the effect of aging which affects the dissolution rates.

Merits over wet granulation process8

The variables faced in the processing of the granules can lead to significant tableting problems. Properties of granules formed can be affected by viscosity of granulating solution, the rate of addition of granulating solution, type of mixer used and duration of mixing, method and rate of dry and wet blending. The above variables can change the density and the particle size of the resulting granules and may have a major influence on fill weight and compaction qualities. Drying can lead to unblending as soluble API migrates to the surface of the drying granules.

Manufacturing steps for direct compression8

Direct compression involves comparatively few steps:

1. Milling of drug and excipients.
2. Mixing of drug and excipients.
3. Tablet compression.

Ramipril (ACE inhibitor), having major disadvantage that on exposure to light and moisture, the degradation9 of ramipril may occur.
The degradation9 of ramipril is believed to occur via two pathways
a)Hydrolysis to ramipril-diacid and
b)Cyclization or condensation to ramipril-diketopiperazine
The stable formulation of ramipril tablet may be achieved by direct compression followed by a special coating technique.
6.2: Review of literature

1. Formulation and evaluation of Enalpril maleate tablet by direct compression technique using lactose DC, Avicel PH 101, talc and starch was done. The Enalpril maleate was evaluated along with six marketed products and it was reported that weight variation, hardness, disintegration, dissolution and assay tests of the same which was prepared by direct compression are within the range10.

1. Formulation and evaluation of Amoxicillin tablets by direct compression technique was done and it was reported that, the type of microcrystalline cellulose has significant influence on hardness, friability and dissolution profiles11.

1. Formulation and evaluation of Naproxen tablets by direct compression technique was done and it was reported that, Naproxen tablets prepared by direct compression using MCC and talcum are helpful in enhancement of flowability, packability, compressibility, compactibility, of pure drug along with enhancement of dissolution profile12.

1. Formulation and evaluation of fast dissolving tablets of Domiperidone by direct compression method was done and it was reported that direct compression method can be considered as an important method for the formulation of fast dissolving tablets of Domiperidone than compared to wet granulation method13.

1. Directly compressible co‐processbile micro‐granules of lactose monohydrate, microcrystalline cellulose and corn starch were formulated and evaluated. It was reported that, these co-processed micro-granules increase the flow property of granules, decrease the disintegration time and increases the binding properties of the dosage form, so these composite particles could be used as a new co‐processed excipients for direct compression14.

1. Film coated (by using Opadry®) Rantidine hydrochloride tablets were formulated and evaluated by direct compression technique using Starch 1500® as a filler disintegrant.It was reported that the tablets produced by direct compression using microcrystalline cellulose and starch 1500® was found to be robust with high mechanical strength and low friability, rapid disintegration and drug dissolution nature15.

1. Ibuprofen tablet formulated by direct compression technique using a novel coprocessed superdisintegrant and it was reportedthat, these tablets proved to be superior to the physical blend in terms of flow due to size enlargement, and also superiority in terms of crushing strength, disintegration time, and drug dissolution16.

1. Orally disintegrating tablets of Famotidine were formulated and evaluated by direct compression method using different superdisintegrants.It was reported that, the tablets formulated by this technique usingcrospovidone and sodium starch glycolate as superdisintegrants exhibited quicker disintegration of tablets than compared to those of L-HPC and croscarmellose sodium17.

1. The formulation and evaluation of orodispersible tablets of Levocetrizine HCl by direct compression and effervescent technique using superdisintegrants reported thatthe direct compression techniquewas most acceptable as compared to effervescent technique.Because the compression of orodispersible tablets by direct compressiontechnique significantly affects the rate of drug release, disintegration time, bioavailability by avoiding first pass metabolism, and found it is economical compared to conventional tablet dosage forms18.

1. The formulation and evaluation oforodispersible Tablets of Ondansetron hydrochloride by direct compression technique using superdisintegrants like sodiumstarch glycolate and croscarmellose sodium was carried out and reported that the tablets which were prepared by direct compression method disintegrated rapidly in oralcavity, had acceptable hardness, friability, and showed improved dissolution rate19.

1. The formulation and evaluation of quick dispersible tablets of Olanzapine by the direct compression technology was carried out and reported that this direct compression method is cost effective20.

1. A work on orodispersible tablets of Buspirone prepared by freeze drying technique and direct compressiontechnique was reported tobe more efficient than wet granulation as; it exhibited fasterdisintegration time when compared to the formulations of wet granulation21.

6.3 Objective of the study:
In the present work attempt will be made to

• To carry out Preformulation studies which includes:

1. Compatibility studies
2. Particle size analysis
3. Flow property of the granules
4. Compressibility and Hausner ratio

• To formulate and evaluate stable form of coated Ramipril tablets, the evaluationincludes:

1. Uniformity in colour, shape, size and film texture
2. Mechanical or tensile strength of the film
3. Weight variation test
4. Friability test
5. Hardness test
6. Disintegration test
7. Dissolutiontest22
8. Stability studies

7.0 Materials and Methods
Drug: Ramipril
Excipients:Excipients will be chosen after studying compatability with active ingredient.
PVA, Glyceral Behanate, Silicified MCC, Croscaremellose sodium,
Sodium stearyl fumarate,Stearyl alcohol, Polyethylene glycol,
Ethylene glycol,Lauryl alcohol, Amylopectin,Stearic acid,Cetyl alcohol,
Compactrol, Sodium hydrogen carbonate, Starch pregelatinized
Lactose, PVP-K30, Magnesium stearte
Method: Direct compression method.
7.1 Source of data:
Data was obtained from Drug invention today, Pubmed, Science direct, Medline,US patent office website& other Internet facilities,various books, literature search and Related Articles from library of The Oxford college of Pharmacy.
7.2 Method of collection of data:
The data will be collected from the prepared formulation on the basis
Formulation of reproducible batches of the preparation.
Evaluation of the formulation consists of

1. Uniformity in colour, shape, size and film texture
2. Mechanical or tensile strength of the film
3. Weight variation test
4. Friability test
5. Hardness test
6. Disintegration test
7. Dissolution test
8. Stability studies

7.3 Does the study require any investigations or interventions to be
Conducted on patients or other humans or animals?
Not applicable
7.4 Has ethical clearance been obtained from your institute in case 7.3?
Not applicable
List of references:

1. Richard F, Michelle AC, Luigi X. Lippincott's illustrated reviews Pharmacology. 4th ed. 2009. p.216.

1. Laurence LB, Keith LP, Donald KB, Iain LOB.Goodman & Gilman's The Pharmacological Basis Of Therapeutics. 11th ed. 2006. p. 301.

1. Diprio JT, Talbert RL, Gary CY, Gary RM, Wells BG, Posey LM.Pharmacotherapy, a pathophysiologic approach, 7th ed. 2008. p. 139-174.

1. TripathiKD. Essentials of Medical Pharmacology, 6th ed. 2008. p. 542.

1. Jain CMK, Valdya S, Jain SK. Utilization of spherical crystallization for preparation of directly compressible materials. J.Indian Drugs. 2004; 41(6). p. 319-29.

1. Lewis S, Udupa N, Atin KD. Solid Dispersions:A ReviewPak.J. Pharm. Sci2009 April;22(2):234-46.

1. The theory and practice of Industrial Pharmacy by Lachman L, Lieberman HA.9thed. 2009; 317-20.

1. Gohel M. Manufacturing methods of tablets. In: pharmainfo.net2009 June 12th.Available from:

1. John HB, John MB. Wilson and Gisvold`s Text book of Organic Medicinal and Pharmaceutical chemistry, 11th ed. 2004. p. 648

1. BB R, Baqir, Naqvi S, Muhammad HS, Rahim N. Design and evaluation of a new formulation of Enalpril maleate.Pak. J. of Pharm. Sci.2011April; 24(2):211-15.

1. Kerly FMP, José ABF, Fabiana EB, Kratz CP. Development and evaluation of amoxicillin formulations by direct compression: Influence of the adjuvants on physicomechanical and biopharmaceutical properties of the tablets.J.Acta farmacéutica bonaerense2005;24:39-47

1. Patra SR, Giri CK, Subrata M. Preparation and physicomechanical characterisation of naproxen tablets by direct compression method.Int. J. of Pharm. Research and Development2011 April;3:193-201.

1. Patel HA, Patel JK, Patel KN, Patel RR. Studies on formulation and in-vitro evaluation of fast dissolving tablets of Domiperidone.Int. J. of Pharm. Sci. 2010 Jan-April; 470-76.

1. Muhammad A, Syed B, Naqvi S, Gauhar S. Development of coprocessed micro granules for direct compression. Int. J. of Pharm. and Pharm. Sci.2011November; 3:64-9.

1. Colorcon®. Direct compression formulation using Starch 1500® with Ranitidine HCl (150 mg) tablets, film coated with Opadry® II (85F Series). 2005 August.

Available from: ver1_aug05.pdf

1. Gohel MC, Parikh RK, Bansari KB, Shah AR. Improving the tablet characteristics and dissolution profile of Ibuprofen by using a novel coprocessed superdisintegrant. J. American Association of Pharm. Sci. and Tech. 2007; 13:E1-E6.

1. Khinchi MP, Bhandari A, Sharma N, Gupta MK, Agarwal D. Design and development of orally disintegrating tablets of Famotidine prepared by direct compression method using different superdisintegrants.J. of Applied Pharm. Sci.2011 January; 1:50-8.

1. Poona, Pandey M, Koshy MK, Saraf S.Preparation and evaluation of orodispersible tablets of Levocetrizine HCl by direct compression and effervescent technique.J. of Pharm. Research 2010 November; 3(11):2697-9.

1. Gosai AR, Patil SB, Sawan KK. Formulation and evaluation of orodispersible tablets of Ondansetron hydrochloride by direct compression using superdisintegrants.Int. J. of Pharm. Sci. and Nanotechnology2008April – June; 1:582-8.

1. Patil SB, Shahi SR, Udavant YK, Atram SC, Salunke RJ, Neb GB. Formulation and evaluation of quick dispersible tablets of Olanzapine. Int. J. of Pharma Research and Development 2009 September;7:1-14.

1. Rajitha K, Shravan Kumar Y, Adukondalu D, Gannu R, Madhusudan RY. Formulation and evaluation of orally disintegrating tablets of Buspirone.International J. of Pharm. Sci. and Nanotechnology 2009January-March; 1:327-34.

1. Indian Pharmacopoeia 2007 5th ed. 2:662-4.

9. / Signature of the Candidate: / (SRINIVAS.MOTURI)
10. / Remarks of the Guide: The above information is true to the best of my knowledge and the work will be done under my guidance.
11. / Name & Designation
11.1 Guide: / Mrs. SURINDER KAUR
11.2 Signature:
11.3 Co-guide: / Mr. SADYOJATHA A.M
DEPUTY GENERAL MANAGER,
FORMULATION, DEVELOPMENT & TRAINING,
BAL PHARMA LIMITED (UNIT 1). BENGALURU.
11.4 Signature:
11.5 Head of the Department / Dr. KALYANI PRAKASAM
11.6 Signature of HOD:
12. / 12.1 Remarks of the Principal: The above mentioned information is correct and I recommend the same for approval. R
12.2 Signature of the Principal / (Dr. PADMAA M PAARAKH)

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