Slide 1: 1 Formulation and Evaluation of Bi-layer tablet : GUIDED BY PRESENTED BY
Dr.V.N.SHRIKHANDE sir Mr. PANKAJ .P.0STWAL
M. PHARM.PhD Student of M. PHARM SEM- 2
Department of pharmaceutics
I.B.S.S.college of pharmacy
2011-2011 2 Formulation and Evaluation of Bi-layer tablet Content : Introduction
Diff.types of Bilayer tablet
Reason of selecting the bilayer
Practical Problem at the time of formulation
Quality and GMP
Plan of work
Reference Content 3 Slide 4: 4 Introduction : Bilayer tableting 5 Introduction + Bilayer tablets can be a primary option to avoid chemical incompatibilities between API by physical separation, and to enable the development of different drug release profiles (immediate release with extended release)1. Advantages : Release of both drugs starts immediately
Combination of incompatible drugs2
Physical/chemical incompatibility can be prevented by physical separation of two drugs.
Combination of different release profiles
Immediate release and sustained release profile can be achieved in single tablet by forming IR layer and SR layer.
Reduced Pill Burden
By reducing individual dose of two drug due to their additive effect.
Example: Salbutamol + Theophylline 6 Advantages Advantages : 7 Advantages Reduce the side effects Reduced by using one drug of the combination for this purpose2.
Amiloride may prevent hypokalemia caused by hydrochlorthiazide19, 20
Elegance to the product Advantages : 8 Advantages Co-morbid Conditions means pertaining to a disease or other pathological process that occurs simultaneously with another18.
Treat different ailments in the same patient (co-morbidity), at the same time and with one pill
Example: Combination of β- blocker and ACE inhibitor or Diuretics is beneficial to treat Hypertention and Heart failure.
Only Allows for synergistic combination Slide 9: 9 Limitations of Bilayer tablet :
Layer Separation Slide 10: 10 Steps of compression of bi-layer tablet :
1. Filling of first layer.
2. Compression of first layer.
3. Ejection of upper punch.
4. Filling of second layer.
5. Compression of both layer together.
6. Ejection of bi-layer tablet Slide 11: 11 Bilayer tablet approach :
Two drugs in same tablet with different layers.
One is immediate release and other is sustained release layer.
Tablet having sustained release layer and floating layer. Ideal candidate of bilayer tablets : Drug produces additive/synergistic effect
Anti- asthmatic: Salbutamol + Theophylline
Drugs having opposite side effects, may reduce the side effect
Omeprazole + NSAIDS
Hydroclorothiazide + Amiloride
Low biological half life (ideal for modified release bilayer)
Unstable at intenstinal pH ( ideal for bilayer floating)
High first pass metabolism with low biological half life (ideal for buccoadhesive bilayer) 12 Ideal candidate of bilayer tablets DIFFERENT TYPES : Bilayer modified release tablet
Aceclofenac9 : NSAIDS, COX-2 inhibitor; t/2 = 3-4 hrs
Metoclopramide HCL + Ibuprofen13, 14:
Metoclopramide HCL is anti emetic; Given as immediate release dose and Ibuprofen is NSAID; given as SR dose, due to its low t/2 (2 hrs).
This is widely used combination in treatment of migraine. It improve the absorbance of Ibuprofen, whose absorption is less due to gastric stasis10 especially in migraine. 13 DIFFERENT TYPES DIFFERENT TYPES : Bilayer floating tablet
Oral anti-diabetic; t/2 = 3-4 hrs; its solubility is decreased by increasing pH.
Β1-selective adrenergic blocker; t/2 = 3-4 hrs; it degraded in colon
ACE inhibitor; 37.5 – 75 mg dose is required in three times; most stable at 1.2 pH. 14 DIFFERENT TYPES DIFFERENT TYPES : Bilayer bucoadhesive tablet
Non-selective β-adrenergic blocker; t/2 = 3-5 hrs; high first pass metabolism.
Drug in buccoadhesive layer, Backing layer is consist of Ethyl Cellulose. 15 DIFFERENT TYPES Slide 16: 16 Reasons for selecting bilayer tablet by pharmaceutical companies
Several pharmaceutical Companies are currently developing multiple layered tablets containing two or more active pharmaceutical materials (or combination therapy) for variety of reasons including:
To get synergistic effects
To inhibit drug interaction
Patent extension Slide 17: 17 Therapeutic justification
To reduce capital investment
To get sustained release tablets preparation in combination, in which generally one layer is in immediate release form and second layer may be extended release form. Practical problems in developing Bilayer tablets : Layer-separation
Order of layer sequence
Layer weight ratio
Elastic mismatch of the adjacent Layers
Cross contamination between layers. 18 Practical problems in developing Bilayer tablets Slide 19: 19 Bi-layer tablets : Quality and GMP-requirements
Preventing capping and separation of the two individual layers that Constitute the bi-layer tablet
Providing sufficient tablet hardness, High yield
Preventing cross-contamination between the two layers
Producing a clear visual separation between the two layers
Accurate and individual weight control of the two layers AIM : To formulate and evaluate the bilayer tablet
To improve the patient compliance towards the therapy.
To minimize the pill burden of the patient AIM 20 Objective of present study : The main objective of present work is to formulate safe, convenience Dosage form which prevent interfere in release profile of both drug with each other.
It is great advantageous to both patient and clinician that medication to be formulated so that it may be administered as a single tablet in once a day.
Improve the patient compliance towards the therapy
Formulation and evaluation of bilayer floating tablets by using optimized immediate and floating sustained release layer. Objective of present study 21 Plan of work : 1. Literature Survey for Review and Research Articles.
2. Experimental Work
iv.Carr’s Index (Compressibility Index) and Hausner’s Ratio
v.Drug Excipients compatibility study
B. Formulation and development of Bilayer Tablet
C. Formula Optimization for bilayer Tablets Plan of work 22 Slide 23: 23 D. Evaluation of Developed Bilayer Tablet
v. Dissolution profiles
vi. Stability of drug Tablets. REFERENCE : Patel Mehul, et al; Challenges in the formulation of bilayered tablets: a review. IJPRD; Vol. 2; 2010, 30-42.
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