The buccal mucosa lines the inner cheek and Buccal formulations are placed in the mouth between upper gingiva(gums) and cheek to treat local and systemic conditions.
Drugs which undergoes Extensive first pass metabolism and drug degradation in acidic media, GI tract can be administered through buccal route.
The oral cavity has been used as a site for local and systemic drug delivery.
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Formulation and evaluation of Muco adhesive Buccal Tablets of Rampril
1. University college of pharmaceutical sciences,
Kakatiya university
Warangal 506009,Telangana,India.
1
Formulation and evaluation of Muco
adhesive Buccal Tablets of Ramipril
Presented by
D.APURUPUA
M.Pharmacy
3rd semester
HT:No:17004p1304
Industrial Pharmacy
Under the guidance
Of
Dr.SHAYEDA
M.Pharm,Ph.D
3. INTRODUCTION
3
Buccal drug delivery system:
īą The buccal mucosa lines the inner cheek and
Buccal formulations are placed in the mouth
between upper gingiva(gums) and cheek to treat
local and systemic conditions.
īą Drugs which undergoes Extensive first pass
metabolism and drug degradation in acidic
media, GI tract can be administered through
buccal route.
īą The oral cavity has been used as a site for local
and systemic drug delivery.
4. ADVANTAGES
4
īą It is richly vascularized and more accessible for the
administration and removal of dosage form.
īą Additionally Buccal drug delivery has good patient
acceptability compared to other non oral routes of drug
administration.
īą Sustained drug delivery.
īą Used in case of unconscious and less cooperative
patients.
īą Avoids acid hydrolysis in GI tract and bypassing the
first pass effect.
īą Some drugs that are unstable in acidic environment of
stomach can be administered by buccal delivery.
īą Rapid onset of action.
5. LIMITATIONS
5
ī Low permeability of the Buccal membrane, specifically when
compared to sublingual membrane.
ī Smaller surface area. The total surface area of membranes of
the oral cavity available for drug absorption is 170 cm2 of
which 50 cm2 represents non-keratinized tissues, including
the buccal membrane.
ī Drugs which are unstable at buccal pH cannot be
administered.
ī Limited absorption of high molecular weight drugs.
6. 6
īDrugs required with small dose can only be
administered.
īDrugs which irritate the mucosa or have a
bitter or unpleasant taste cannot be
administered by this route.
īDrugs contained in the swallowed saliva follow
the pre-oral and advantages of buccal route are
lost.
8. BIOADHESIVE POLYMERS
8
Ideal characteristics:
īą The polymer and its degradation products should be
non-toxic, non-irritant to the mucous membrane.
īą It should adhere quickly to moist tissue.
īą The polymer must not decompose on storage or during
the shelf life of the dosage form.
īą It should allow easy incorporation of drug into
formulation.
Polymers used in muco adhesive dosage forms:
Natural polymers: gelatin, sodium alginate, guar gum,
chitosan.
Synthetic polymers: PVA, PEG, HPMC, PVP, sodium
CMC, Carbomers etc.
9. THEORIES OF MUCOADHESION
9
īąElectronic theory: muco adhesive and biological
materials possess opposite electrical charges
īąAdsorption theory: muco adhesive devices adheres
to mucus by vander Waal forces, hydrogen bonds,
electrostatic attractions and hydrophobic interactions
īąWetting theory: applies to liquid systems which
present affinity to the surface inorder to spread over it
10. 10
īąDiffusion theory: interpretation of both polymer and
mucin chains to sufficient depth to create a semi-
permanent adhesive bond
īąFracture theory: studies on mechanical measurement
of muco adhesion
īąMechanical theory: adhesion to be due to filling of
irregularities on a rough surface by muco adhesive
liquid
11. BUCCAL TABLETS
11
ī Tablets are small, flat and oval with a diameter of
approximately 5-8mm.
ī Buccal adhesive tablets are held between the gum and
cheek.
ī Several bio adhesive buccal formulations were
developed by direct compression method in recent years
either for systemic or local drug delivery.
ī Tablets that are placed directly onto the mucosal
surface have been demonstrated to be excellent bio
adhesive formulation.
ī However, size is a limitation for tablets due to
requirement for the dosage form to have intimate
contact with mucosal surface.
12. LIST OF DRUGS USED IN BUCCAL
TABLETS
12
Drug Drug
Nifedipine Micanazole nitrate
propanolol Carbamazepine
Danazol Acyclovir
Piroxicam Pentazocine
Theophylline Diclofenac sodium
Omeprazole Hydrocartisone acetate
15. 15
īļ S.Velmurugan et al,(2011) to prepare and characterize
buccoadhesive tablets of Metoprolol tartrate using different
Mucoadhesive polymers such as Carbopol 934, Sodium alginate and
HPMC K4M in combination. The prepared tablets were evaluated.
the formulation F8 containing carbopol 934 and HPMCK4M in the
ratio of 1:1.25 was showed optimum bioadhesive strength and
exhibited optimum drug release (77.33Âą0.23).
īļ Himabindu et al,(2012) buccco adhesive bilayered tablets of
Eletriptan hydrobromide prepared by using HPMCK4M, Carbopol
941NF and Carbopol 974P as mucoadhesive polymers with varying
concentration. The formulation were evaluated. Optimized
formulation F3 of HPMCK4M showed maximum release of the
drug(97.83Âą0.41)and permeated 73.52 of the drug through porcine
Buccal membrane.
16. 16
īļ Anup Kumar Roy et.,al(2013) to formulate and study mucoadhesive
buccal tablets of Valsartan using various suitable bioadhesive polymers such
as CP 934, HPMC K4M, and Na CMC. Mucoadhesive buccal tablets of
Valsartan were prepared by direct compression method. The prepared tablets
were evaluated. It was found that swelling index was proportional to CP and
Na CMC content. As the Na CMC content increases the swelling index also
increased. The formulation F3 containing CP:HPMC in the ratio 1:3 was
considered as the optimized formulation based on satisfactory bioadhesive
strength, In-vitro dissolution drug release of 59.69 Âą 0.95%, In-vitro drug
diffusion of 43.66 Âą 0.68% for 8 h.
īļ Iman S. Jaffar, Nidhal K. Maraie (2014) Tablets of Promethazine HCl
were prepared by direct compression method using carbopol 940P primary
polymer and sodium alginate, sodium CMC and HPMC K15M as secondary
polymers. The tablets were evaluated. The formula that contains carbopol
940P as primary polymer in concentration(3% w/w) and sodium alginate as
secondary polymer in concentration (27% w/w) was found to be pH value
(6.11), mucoadhesive strength (15.6Âą0.62gm), residence time (7.45 hr),
cumulative percent drug release was 88 % after 6 hr. F1 selected as
optimum formulation.
17. 17
īļ Niranjan Panda et al,(2015) Sumatriptan Succinate Mucoadhesive
Buccal tablet prepared by direct compression method using
Mucoadhesive polymers such as HPMC K4M, Carbopol 934P, ethyl
cellulose and guar gum. The prepared tablets were evaluated for
different parameters. Ex vivo mucoadhesive strength, and in vitro
release studies showed that formulation SMF12 containing 12.5% of
each polymer combination showed satisfactory bioadhesive strength
and exhibited optimum drug release (99.33% after 10hrs).
īļRelin Mariya Raichan et al,(2016) Nifedipine Mucoadhesive
Buccal tablets were prepared by direct compression method using
different polymers such as carbopol 940, HPMC E15, PVP K30,
Sodium CMC, HEC. Prepared tablets were evaluated for different
parameters. By using carbopol 940 and sodium CMC in 1:2 ratio
showed 98.8% drug release. In order to increase the bioavailability to
avoid the hepatic metabolism, the mucoadhesive buccal tablets of
Nifedipine were prepared.
18. DRUG PROFILE:
18
ī Drug name : Ramipril
ī Synonym : Altace
ī Molecular formula : C23H32N2O5
ī Molecular weight : 416.511g/mol
ī Dose : 2.5 to 20 mg/day
ī Category : Angiotensin converting enzyme
inhibitor
19. 19
ī IUPAC name : (2S,3aS,6aS)-1-[(2S)-2-[[(2S)-1-
ethoxy-1-oxo-4-phenylbutan-2-
yl]amino]propanoyl]-3,3a,4,5,6,6a-hexahydro-
2H-cyclopenta[b]pyrrole-2-carboxylic acid
ī Mechanism of action : lowering production of angiotensin â Ą
ī Solubility : BCS class â Ą drug soluble in water(<1 mg/ml),
solvents like DMSO, methanol, aqueous
alkali, ethanol.
ī Melting point : 109áĩc
ī Log P : 2.9
21. RATIONALE FOR DRUG SELECTION:
21
īą Ramipril is an angiotensin -converting enzyme (ACE)
inhibitor. It is used alone or together with other medicines
to treat high blood pressure(hypertension).
īą It works by blocking a substance in the body that causes
blood vessels to tighten. As a result ramipril relaxes blood
vessels.
īą It undergoes extensive first pass metabolism.
22. 22
īąIts bioavailability when given by oral route is
28% due to low solubility and half life is 2 to 4
hrs.
īąSo, in order to improve bioavailability and to
avoid the hepatic first pass metabolism , the
study has been planned to prepare Ramipril
Buccal tablets
23. AIM AND OBJECTIVE
23
ī The main aim of this study is to formulate and evaluate
muco adhesive buccal tablets of ramipril using various
muco adhesive polymers for bypassing its hepatic first
pass metabolism and to enhance bioavailability of drug.
Objective of the study:
īą To develop muco adhesive buccal tablets of Ramipril by
using muco adhesive polymers in different ratios.
īą To characterize the developed systems for
physicochemical properties, in vitro release and all
possible evaluation parameters.
24. PLAN OF WORK
24
ī In order to meet the aim and objective, the work is planned
in the following manner.
pre formulation studies :
ī Preparation of standard curves of Ramipril in water,
Phosphate buffer pH 6.8 and Phosphate buffer pH 7.4
ī Solubility studies
ī Determination of Drug- Excipient Compatibility using DSC
studies.
ī To develop Muco adhesive tablets for the drug using muco
adhesive polymers by Direct Compression method.
ī To evaluate Muco adhesive buccal tablets.
26. MATERIALS
26
Name Source
Ramipril KP labs ,Hyderabad
Guar gum Finar limited
Sodium alginate Sigma Chemicals Ltd,
New Delhi
PVP K30 Finar limited
PEG 6000 SD Fine Chemicals Ltd
Aspartame Hi media chemicals
Magnesium sterate Hi media chemicals
Talc Hi media chemicals
Potassium dihydrogen
orthophosphate
SD Fine Chemicals Ltd
Sodium hydroxide pellets SD Fine Chemicals Ltd
Mannitol SD Fine Chemicals Ltd
Methanol SD Fine Chemicals Ltd
27. S.NO
Equipment Manufacturer
1 Rotary tablet machine Riddhi,Ahmedabad
2 Digital weighing balance Schimadzu
Corporation , Japan
3 Monsanto hardness tester Cadmach ,
Ahmedabad
4 Friabilator (USP) Electro lab, Mumbai
5 Dissolution apparatus Electro lab, India
6 UV-Visible
Spectrophotometer
Systronics-117,
India
7 DSC Perkin Elmer
8 Digital pHmeter Global Electronics,
Ltd
9 Mechanical stirrer Bandelin Sonorex
27
EQUIPMENTS
28. METHODOLOGY
28
Preparation of buccal tablets:
DIRECT COMPRESSION METHOD:
Accurately weighed quantity of Ramipril
(2.5mg of drug) was mixed manually with
different ratios of polymers. Then the powder
blend was compressed into tablets by Direct
Compression method using 6mm flat faced
punches. The tablets were compressed using
sixteen station rotary tablet-punching machine.
29. EVALUATION TESTS
29
īą Weight variation
īą Thickness
īą Hardness test
īą Friability test
īą Content uniformity test
īą Surface pH
īą Swelling studies
īą in-vitro drug release studies
īą Bio adhesive strength
īą ex-vivo residence time
īą ex-vivo permeation studies
īą Stability studies
īą in-vivo studies
30. REFERENCES
30
ī S. Kuppuswamy, Relin Mariya Raichan. Formulation and
Evaluation of Mucoadhesive Buccal tablets of Nifedipine.
International Journal of Institutional Pharm & Life Sciences
2016,6(4), 337-358.
ī Iti Karia, Dr. Ramesh, B. Parmar Formulation and Evaluation
of Fast dissolving tablets of Olmesartan Medoxomil by using co
processed excipients techique World Journal of Pharmacy and
Pharmaceutical Sciences Vol 4, Issue 05, 2015.
ī Iman S. Jaffar Nidhal K. Maraie Formulation and In vitro
Evaluation of Buccal Mucoadhesive Tablets of Promethazine
HCL. International Journal of Pharmaceutical Sciences Review
and Research, 24: 2015 ,61-69.
31. 31
âĸKarimunnisa Shaik, Shanmugam V, Avinash Angilicam,
Sivakoteswara Rao, Formulation and Evaluation of Famotidine
Buccal tablets. International Journal of Innovative Pharmaceutical
Research, 05: 2014,410-417.
âĸAnup Kumar Ray, Vinod Kumar S.M. Syed Jalaluddin Basha,
Rabiul Haque, Roopa Karki Formualtion and Evaluation of
Mucoadhesive Buccal tablets of Valsartan. International Drug
Development &Research., 5(4): 2013,145-155.
âĸS. Himabindu, D. Sathish, Shaik Shayeda et al, Formulation
and Ex vivo evaluation of Buccal tablets of Eletriptan
Hydrobromide. Am. Journal Pharm Technology Resarch; 2012.
âĸParth S. Patel, Ashish M. Parmar. Buccal Bioadhesive Drug
Delivery system: An overview. International Journal Drug
Development& Resarch ;2013,5(3):35-48.
32. 32
âĸS. Velumurugan, K. Naga Raju, B. Deepika, Sundar Vinushitha
Formulation and in vitro evaluation of Buccal tablets of Metoprolol
tartrate. International Journal of Pharmaceutical Sciences;2011, 239-246.
âĸ Ravi Krishna. Y. Madhusudhan Rao, Chinna Reddy.K, Sujatha.,
Formulation and in-vitro Evaluation of Buccoadhesive tablets of
Furosemide. International Journal of Drug Development & Research. Vol.
3,2011, 351-361.
âĸJain NK. Controlled and Novel Drug Delivery,1st edition 2009 reprint,
CBS publisher, New Delhi.