Bilayer Floating Technology: An Innovative Approach

 

Sonawane Pradnya L.1*, Darekar A. B.1, Saudagar R. B.2

1Department of Pharmaceutics, R. G. Sapkal College of Pharmacy, Anjaneri, Nashik-422213, Maharashtra, India.

2Department of Pharmaceutical Chemistry, R. G. Sapkal College of Pharmacy, Anjaneri, Nashik-422213, Maharashtra, India.

*Corresponding Author E-mail: pradnya88062@gmail.com

 

ABSTRACT:

The recent patented literature has concluded that there is an increasing interest in the novel dosage forms which retained in stomach for a longer period of time. Bilayer floating drug delivery system is new era for development of controlled release formulation. Bilayer floating drug delivery system is combined principle of bilayer technology as well as floating tablet is suitable for two incompatible drugs.  The dosage form contains one sustain release layer and other is immediate layer. The immediate release layer is used to maintain dose. The floating dosage form can be prepared as tablet, capsule by adding suitable ingredients as well as adding gas generating agents.

 

KEYWORDS: Gastroretentive dosage forms, Bilayer floating drug delivery system, Immediate layer, control release layer.

 

 


INTRODUCTION:

Drug delivery system has an aim to provide long as well as nontoxic concentration in blood as well as in various tissues that should be therapeutically active. Today various drug delivery system are available in market among which most commonly used is oral drug delivery system. Among oral route 90% of drugs are administered which provides a very good systemic effect. Solid oral dosage forms are more stable through which tablets are most common solid oral dosage forms.

 

The concept of floating drug delivery system (FDDS) was described in literature as early as 1968.Gastric floating drug delivery system (GFDDS) offer numerous advantages over gastric retentive system. This system has a low density than gastric fluids and thus remain buoyant in stomach without affecting gastric emptying rate for a longer period of time.

While the dosage form is floating over the gastric contents, the release of drug is slow. Floating dosage forms are oral dosage forms of tablet, capsule, or micro beads and contain hydrocolloids that allows floating by swelling thereby prolong the residence time of dosage form GIT.

 

Anatomy of stomach(1-4)

The main function of stomach is process and transport food. It works as a short term reservoir. As food is liquefied in stomach, it is slowly released into small intestine. The stomach is divided in 3 regions: Fundus, body, and antrum. The cardiac sphincter is a specialized valve found between the esophagus and the stomach. It prevents backflow of food and digestive enzymes. The fundus is the frontal region of the stomach. It begins digestion of proteins and mixes together stomach contents. The body is the central region of the stomach. It also digests proteins and blends materials found in stomach. The pylorus is the back region of the stomach. It contracts to empty materials from the stomach into the small intestine.


 

Fig 1: Anatomy of stomach

 

Fig 2: Type of tablet for oral Ingestion.

 


Needs of gastric retention.(6):

·         Particularly used for the treatment of peptic ulcer caused by H. Pylori infection.

·         Local and sustained drug delivery to small intestine and stomach to treat certain conditions.

·         Drugs that are less soluble or are degraded by alkaline pH they encounters at lower part of GIT.

·         Drugs that are absorbed due to variable gastric emptying time. Drugs that are absorbed from proximal part of gastrointestinal tract (GIT).

 

Classification of floating drug system(6-14):

A. Non-effervescent system.

a.       Colloidal gel barrier system.

b.       Bilayer floating tablet.

c.        Microporous compartment system.

d.       Alginate beads.

e.        Hollow microspheres.

 

B. Effervescent system.

a.       Volatile liquid containing system.

b.       Gas generating system. 

 

A. Non-effervescent:

After swallowing the dosage form swells with the inhibition of gastric fluidin such manner that its exist from stomach is avoided. Due to the drug mixed with gel it get swell when it comes in contact with gastric fluid and the shape is maintained. That remain near the pyloric sphincter due to this it is also called as plug-type system. The bulk density of dosage form must be <1. Gel forming and swellable cellulose type of hydrocolloids, polysaccharides and matrix formingpolymers like polyacrylate, polystyrene, polycarbonate,carbopol, sodium alginate and polymethacrylate are used in non-effervescent system.

 

a.       Colloidal  gel barrier system

Hydrodynamically balanced system first designed by Sheth and Tossounian. They remain in the stomach buoyant and form gel due to hydrocolloids and enhances GRT and also increase the amount of drug at absorption site.various agents used for gel forming are hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polysaccharides and matrix forming polymers such as polycarbophil, polystyrene.

 

b.       Bilayer Floating Tablets

This system basically have tablet basically have two layer one is immediate layer and other is sustain release the immediate release layer release initial dose immediately and sustain release forms a colloidal gel barrier by absorbing gastric fliud.so it maintain density less than1. And remain floating in stomach.

 

c.        Microporous compartment system

In Micropororous compartment system it has pores on the top and on bottom walls that contains encapsulated drug reservoir. Through an aperture the gastric fluid enters that dissolve drug for absorption across intestine.

 

d.       Alginate Beads

By freeze-dried calcium alginate multi-unit floating dosage have been developed. By precipitation method spherical beads of approximately 2.5 mm have been prepared by dropping sodium alginate solution into aqueous solution of calcium chloride.

 

e.        Hollow Microspheres.

The method used for preparation of hollow microsphere loaded with drug is solvent evaporation method emulsion solvent diffusion method. The buoyancy and drug release for a dosage form depends mainly on quantity of polymer, solvent system and plasticizer to polymer ratio. The polymer used are eudragit S, cellulose acetate, polycarbonate, pectin.

B. Effervescent:

Various type of polymers are used such as a chitosan and methylcellulose and effervescent material such as citric acid, tartaric acid, calcium carbonate. This system when come in contact with acid gastric content of stomach that liberates carbon dioxide and in swollen hydrocolloids it get entrapped and provide buoyancy to the dosage form.

 

a.       Volatile Liquid Containing

Due to Inflatable chamber with which  a liquid can be incorporated and provide sustained gastric retention of drug delivery system. Liquids in this system include, ether that gasifies atbody temperature which causes inflatation of the chamber in the stomach.  They contain hollow deformable unit which are osmotically controlled floating systems. System is divided into two compartment first compartment contains drug and there is volatile liquid in the second compartment.

 

b.       Gas Generating System

It basically containsa polymer that gasifies at body temperature effervescent compounds such as sodium bicarbonate, citric acid, tartaric acid, swellable polymers like methocel, polysaccharides like chitosan. Resin beads loaded with bicarbonate and coated withethylcellulose is the most common approach for preparation of these systems. The ethycellulose coating is insoluble but permeable to water which release carbon dioxide due towhich it float.


 

Fig 3: Classification of floating system.

 


Drugs that are not used for GRRDS

1.Drug which have very limited acidic solubility. eg. phenytoin.

2.Drugs that face instability in the gastric environment. eg .Erythromycin.

3. Drugs that are intended for the selected release in colon.eg. Corticosteroids.

 

Advantages of floating drug delivery System.(1-5)

1.The principle of HBS can be used for any medicament or class of medicaments.

2.The HBS are advantage for drugs absorbed through stomach eg. ferrous salts and for drugs meant for local action in the stomach and treatment of peptic ulcer disease e.g. antacids.

3.  The efficacy of the medicaments administered utilizing the sustained release principle of HBS has been found to be independent of the site of absorption of the particular medicaments.

5. Administration of a prolonged release floating dosage form tablet or capsule will result in dissolution of the drug in gastric fluid.

6. When there is vigorous intestinal movement and a short transit time, poor absorption is expected under such circumstances it may be advantageous to keep the drug in floating condition in stomach to get a relatively better response.

7. The delivery of drugs with narrow absorption windows in the small intestinal region.

8. Many drugs categorized as once-a day delivery have been demonstrated therefore, a system designed for longer gastric retention will extend the time within which drug absorption can occur in the small intestine.

9. Certain types of drugs can benefit from using gastro retentive devices.

 

Disadvantages of floating bilayer tablet:

1.Not applicable to drugs which are irritant to gastric mucosa.

2.Floating systems are not feasible for those drugs that have solubility.

3.Drug Substances that are unstable in acidic environment of stomach are not suitable candidates to be incorporated in the system.

4.These system require a high level of fluid in stomach for drug delivery to float and work efficiently.

5.Capping is another major problem with bilayer tablets.

6. Separation of two layers may occur due to insufficient bonding and reduction in yield occurs.

7. Hardness is other problem.

8. There are chances of cross contamination between two layers.

9. Because of low density and amorphous nature of some drugs compact do not form as they resist compression.

10.The control over weight of individual layer is less.

11.Swallowingproblem in case of unconscious patient and children.

12. Bioavailability problems may occurs in the case of poor wetting and less dissolution properties.

13. Most often encapsulation or coating is required for the drugs that are oxygen sensitive, bitter tasting and with bad odour.

 

Criteria for selection of drug for floating bilayer tablet.

1.Molecular size- smaller than 100-600 Dalton.

2.Drugs that have acidic solubility.

3.Drugs that have narrow absorption window in GIT.

4.Drugs that are locally active in stomach environment.

5.Administered two or more time a day.

 

Factors affecting floating drug delivery system (16,17)

Various attempts have been made to retain the dosage form in the stomach as a way of increasing the retention time. These attempts include use of floating dosage forms (gas generating systems and swelling or expanding systems), mucoadhesive systems, high density systems, modified shape systems, gastric-emptying delaying devices and coadministration of gastric-emptying delaying drugs. Most of these approaches are influenced by a number of factors that affect their bioavailability and efficacy of the gastro retentive system:

 

• Density

Gastric retention time (GRT) is a function of dosage form buoyancy that is dependent on the density.

 

• Size

Dosage form units with a diameter of more than 7.5 mm are reported to have an increased GRT compared with those with a diameter of 9.9 mm.

 

• Shape of dosage form

Tetrahedron and ring shaped devices with a flexural modulus of 48 and 22.5 kilo pounds per square inch (KSI) are reported to have better GRT 90% to 100% retention at 24 hours compared with other shapes.

 

• Single or multiple unit formulation

Multiple unit formulations show a more predictable release profile and insignificant impairing of performance due to failure of units, allow co-administration of units with different release profiles or containing incompatible substances and permit a larger margin of safety against dosage form failure compared with single unit dosage forms.

 

·         Fed or unfed state

Under fasting conditions, the GI motility is characterized by periods of strong motor activity or the migrating myoelectric complex (MMC) that occurs every 1.5 to 2 hours. The MMC sweeps undigested material from the

stomach and, if the timing of administration of the formulation coincides with that of the MMC, the GRT of the unit can be expected to be very short. However, in the fed state, MMC is delayed and GRT is considerably longer.

 

• Nature of meal:

Feeding of indigestible polymers or fatty acid salts can change the motility pattern of the stomach to a fed state, thus decreasing the gastric emptying rate and prolonging drug release.

• Caloric content:

GRT can be increased by four to 10 hours with a meal that is high in proteins and fats.

 

• Frequency of feed:

The GRT can increase by over 400 minutes when successive meals are given compared with a single meal due to the low frequency of MMC.

 

• Gender

Mean ambulatory GRT in males (3.4±0.6 hours) is less compared with their age and race matched female counterparts (4.6±1.2 hours), regardless of the weight, height and body surface).

 

• Age

Elderly people, especially those over 70, have a significantly longer GRT.

 

• Posture

GRT can vary between supine and upright ambulatory states of the patients.

 

Polymers used in floating drug delivery.(15)

Sustained Release Polymers are HPMC K100M, HPMC K15M, HPMC ELV, Polycarbonate, Polyethylene glycol, Sodium alginate, Carbopol, Eudragit. Effervescent Generating System: Citric and Tartaric Acid, Sodium Bicarbonate, Citroglycine. Polymers which increase buoyancy: Ethyl Cellulose Polymers which decrease release: Talc, Magnesium Stearate, Dicalcium Phosphate. Polymers which increase release: Mannitol, Lactose. Inert Polymers: Long Chain Fatty Alcohol, Fatty Acid, Beeswax. Polymers with low density: Foam powder of polypropylene.

 

Sustain Release Polymer

HPMC K100M, HPMC K15M, Polycarbonate, polyethylene Glycol, Sodium Alginate, carbopol, Eudragit.

Effervescent generating system

Citric acid, Tartaric acid, Sodium bicarbonate, citroglycine.

Polymer which increases buoyancy

Ethylcellulose.

Polymer which decrease release

Talc, Magnesium Stearate, Dicalcium phosphate.

Polymer which increases release

Mannitol, Lactose.

Inert polymer

Long chain fatty alcohol, Fatty acid, Beeswax.

Polymer with low density

Polypropylene.

Fig 4:Polymers used in floating drug delivery system.

 

Mechanism of floating system:(5,7)

FDDS has a bulk density less than gastric fluids and so remain buoyant in the stomach without affecting the gastric empting rate for a prolonged period of time.

 

F= F buoyancy – F gravity = ( Df- Ds) gv

 

Where,

F= total vertical force, Df= fluid density,

Ds= object density, v =volume, g = acceleration due to gravity.

 

Fig 5: Mechanism of floating.(18)

 

Various technologies involved in bilayer tablets:-(19-25)

A.      OROS push and pull technology.

B.      L-OROS tm technology.

C.      EN SO TROL technology.

D.      DUROS technology.

E.       Elan drug technology ‘dual release drug delivery system.

 

A.    OROS push and pull technology.

This system consist of mainly two or three layers among which one or more layers are essential of the drug and other layers are consist of push layer. The drug layer mainly consists of drug along with two or more different agents. So this drug layer comprises of drug which is in poorly soluble form. There is further addition of suspending agent and osmotic agent. A semi permeable membrane surrounds the tablet core.

 

B.    L-OROS tm technology.

L-OROS tm technology This system used for the solubility issue Alza developed the L-OROS system where a lipid soft gel product containing drug in a dissolved state is initially manufactured and then coated with a barrier membrane, than osmotic push layer and then a semi permeable membrane, drilled with an exit orifice.

 

C.    EN SO TROL technology.

Solubility enhancement of an order of magnitude or to create optimized dosage form shire laboratory use an integrated approach to drug delivery focusing on identification and incorporation of identified enhancer into controller release technologies.

 

D.    DUROS technology.

Solubility enhancement of an order of magnitude or to create optimized dosage form shire laboratory use an integrated approach to drug delivery focusing on identification and incorporation of identified enhancer into controller release technologies.

 

E.    Elan drug technology ‘dual release drug delivery system

The system consists from an outer cylindrical titanium alloy reservoir (Fig. 3).This reservoir has high impact strength and protects the drug molecules from enzymes. The DUROS technology is the miniature drug dispensing system that opposes like a miniature syringe and reglious minute quantity of concentrated form in continues and consistent from over months or year.


 

Characterization of floating bilayer tablets:

Pre-compression Parameters.( 16, 27, 23, )

Test

Method

1.        Angle of Repose

Angle of repose is used to measure powder frictional forces. Calculated by the formula,

 

tanΘ= h/r

Θ=tan-1h/r

 

Where Θ = Angle of repose

h= height of pile

r=radius of pile

Flow property according to angle of repose is

Angle of repose Powder flow

Angle of repose

Powder flow

<25

Excellent.

25-30

Good

30-40

Passable

>40

Very poor

2.Compressibility index

Compressibility index is calculated by formula,

 

Compressibility index (%) = ρt – ρo* 100 / ρt

 

Where ρt = Tapped density gram/ml

ρo = Bulk density gram/ml

 

3.Bulk Density

It is defined as mass of powder divided by bulk volume ,and it is dented by ρb

Method: 50 cm3 of powder has been taken is passed through sieve no.20 which isthe introduced in 100 ml graduated cylinder. The cylinder is allowed to tapped onhard wood surface for about 500 times.

 

4. Tapped Density

Tapped density is calculated by the formula,

 

Tapped density= Weight of powder taken/ Tapped Volume

 

5.Particle Size Distribution

By sieving method

 

 

Post- Compressibility Parameters.(6, 7, 12, 17, 18, 20,21,  23, )

TEST

METHOD

1.Shape of tablet

Tablet shape is checked by magnifying lens after compression.

2.Tablet dimension

In this three tablets are randomly taken and then their thickness and diameter are measured by verniercalliper or by using calibrated screw gauze.

3.hardness

Twenty tablets are selected and weighed individually. Then the average weight and standard deviation is calculated. Test passes when not more than two tablets deviate from average weight.

LIMIT OF WEIGHT VARIATION

weight

% variation

Less than 80 mg

10%

80-250mg

7.5%

Above 250 mg

5%

4.Friability

10 tablets are selected and weighed and then they are  placed in friabilator apparatus

which rotate at 25 rpm speed for 4 minutes. After 4 minutes tablets are weighed again.

 

%F=[1-(Wt/W)]*100

 

W – Initial weight of tablet

Wt- Weight of tablet after revolution.

If % Friability of tablets is less than 1% is considered acceptable.

s5.Disintegration test

In this one tablet is placed in disintegration apparatus containing buffer 0.1 N HCl or PBS pH 6.8 and test is carried out at 37°C. The time taken by tablet to disintegrate is noted as disintegration time.

6.In vitro Dissolution

Dissolution study is performed using USP paddle apparatus by maintaining optimum temperature i.e. 370ºC at 50 rpm rotational speed. At various time interval 5 ml sample is withdrawn and is replaced with same amount of buffer.

7.Floating Lag Time

It is the time interval taken by the tablets to start floating. It should be less than one minute. It is measured by dissolution test apparatus containing 0.1 N HCl(900ml).

8.Floating time

It is the total time taken by which the tablets remain floating in the media.

9.Drug Content Uniformity

Ten tablets are taken and powdered equivalent weight of drug dose is taken andis transferred to volumetric flask and then buffer is added and absorbance isdetermined using U.V spectrophotometer.

10.Specific gravity

The displacement method is used in which benzene is used as displacing medium to determine the specific gravity of floating system.

 

 

 


In-vivo evaluation:-(25-33)

a) Radiology:

X-ray is widely used for examination of internal body systems. Barium Sulphate is widely used Radio Opaque Marker. So, BaSO4 is incorporated inside dosage form and X-ray images are taken at various intervals to view gastric retention.

 

b) Scintigraphy:

Similar to X-ray, emitting materials are incorporated into dosage form and then images are taken by scintigraphy. Widely used emitting material is 99Tc.

 

c) Gastroscopy:

Gastroscopy is peroral endoscopy used with fiber optics or video systems. Gastroscopy is used o inspect visually the effect of prolongation in stomach. It can also give the detailed evaluation of GRDDS.

 

d) Magnetic Marker Monitoring:

In this technique, dosage form is magnetically marked with incorporating iron powder inside, and images can be taken by very sensitive bio-magnetic measurement equipment. Advantage of this method is that it is radiation less and so not hazardous.

 

e) Ultrasonography:

Used sometimes, not used generally because it is not traceable at intestine.

 

f) 13C Octanoic Acid Breath Test:

13C Octanoic acid is incorporated into GRDDS. In stomach due to chemical reaction, octanoic acid liberates CO2 gas which comes out in breath. The important Carbon atom which will come in CO2 is replaced with 13C isotope. So time up to which 13CO2 gas is observed in breath can be considered as gastric retention time of dosage form. As the dosage form moves to intestine, there is no reactionandno CO2 release. So this method is cheaper than other.

 

 

CONCLUSION:

Floating bilayer drug delivery system may be used for various active agents with the narrow absorption window that are absorbed from specific region of GI tract .pharmaceutical industries are trying to prepare one of the most economic and conventional dosage form the floating bilayer tablet is the best then any other approach. Through floating bilayer tablets both type of release i.e. sustain as well immediate release can be obtained and sustain release can be increased upto 24 hours. The currently available polymer mediate Non-effervescent and effervescent FDDS.

 

Some of the unresolved critical issues related to the rational development of FBDDS include, the quantitative efficiency of floating delivery systems in the fasted and fed states and the correlation between prolonged GRT and SR/PK characteristics. In addition, by continual supplying the drug to its most efficient site of absorption, the dosage form may allow for more effective oral use of peptide and protein drugs such as calcitonin, erythropoetin, vasopressin, insulin, low molecular weight heparin, and LHRH.

 

REFERENCES:

1.        Kumara PJ, Ramarao T and Jayaveera KN. Review on bilayer floating tablets – a novel approach to gastroretention. Ind Am J Pharm Sci. 2013;3(5):2231-76.

2.        Shrikant M, Shah S and Upadhyay P. Floating Bilayer drug delivery system- An Unconventional approach in Conventional Form. Am J PharmTech Res. 2012;2(2):2249-87.

3.        Dutta P, Sruti J, Patra NC and Rao BME. Floating microspheres: Recent trends and development of gastroretentive floating drug delivery system. International Journal

1.        Pharmacy Science Nanotechnology. 2011;4(1):1296-306.

4.        Pujara ND, Gokani RK and Paun JS. Bilayer tablet- an emerging trend. Int J Pharm Res Dev. 2011;4(4):102-11.

5.        Hardenia SS. Floating Drug Delivery Systems: A Review Asian J of Pharmacy and Life Sci. 2011;1(3):96-106.

6.        Christian V, Ghedia T and Gajjar V. A Review on Floating Drug Delivery System As A Part of GRDDS. Int J Pharm Res Dev. 2011;3(6):233 – 241.

2.        7.Deshpande RD, Gowda DV, Mohamad N, Marambar DN. Bi-Layer Tablets- An Emerging Trend: A Review. International Journal of Pharmaceutical Science and Research 2, 2011, 2534-2544.

7.        Dixit N. Floating Drug Delivery System. Journal of Current Pharmaceutical Research 7, 2011, 6-20.

8.        Mayur AC, Senthilkumaran K, Gangurde HH, Tamizharasi S. Floating Drug Delivery System: A Versatile Approach for Gastric Retention. International Journal of Pharmaceutical Frontier Research 1, 2011, 96-112.

9.        Gopalakrishnan S, Chenthilnathan A. Floating Drug Delivery Systems: A Review. Journal of Pharmaceutical Science and Technology 3, 2011, 548-554.

10.     Amit KN, Ruma M, Biswarup D. Gastroretentive drug delivery systems: a review. Asian Journal of Pharmaceutical and Clinical research 3, 2010, 345-349.

11.     Mayavanshi AV, Gajjar SS. Floating drug delivery systems to increase gastric retention of drugs: A Review. Research J. Pharm. and Tech 1, 2008, 345-348.

12.     Soni RP, Patel AV, Patel RB, Patel MR, Patel KR, Patel NM. Gastroretentive drug delivery systems: A Review International Journal of Pharma World Research 2, 2011.

13.     Mahale GS, Derle ND. Floating Drug Delivery System: A Novel Approach. Journal of Pharmaceutical and Scientific Innovation 1, 2012, 1-6.

14.     Sarojini S, Manavalan R. An overview on various approaches to Gastroretentive dosage forms. Int. J. Drug Dev. & Res 4, 2012, 01-13.

15.     Shaikh TK, Gadhave MV, Jadhav SL, Gaikwad DD. Different Techniques of Bilayer Tablet: A Review. International Journal of  Universal Pharmacy and Life Sciences 2, 2012, 450-460

16.     Chandira RM, Palanisamy P, Jayakar B. Formulation and Evaluation of Bilayered Floating tablets of Metformin Hydrochloride. International Research Journal of Pharmacy 3, 2012, 257-266.

17.     Gahiwade HP, Patil MV, Thakare BW, Vinod MT, Patil VR. Formulation and In-vitro evaluation of TrifluperazineHcl bilayer floating tablets. International Journal of Pharma and BioScience 2, 2012, 166-172.

18.     Narendra C, Srinath MS, and Ganesh B. Optimization of Bilayer Floating Tablet containing Metoprolol Tartrate as a Model Drug for Gastric retention. AAPS PharmaSciTech 7, 2006, 1-17.

19.     Kumar MV, Krishnarajan D, Manivannan R, Parthiban KG. Formulation and evaluation of bi-layer domperidone floating tablets. International journal of Pharmaceutical sciences and

3.        Research 2, 2011, 2217-2225.

20.     Dinakaran SK, Formulation and evaluation of bi-layer floating tablets of ziprasidone HCl and trihexyphenidyl HCl, Brazilian Journal of Pharmaceutical Sciences 4, 2011, 545-555.

21.     Indian Pharmacopoeia.2nd edition, Published by the Controller Publication, Delhi, 1996, 736.

22.     The United States Pharmacopoeia, United states Pharmacopoeial convention, Inc., Rockville, MD, 2000:1944.

23.     Lokendra PS, Rakesh KS, Deepak GU, Vijay KC, Viral KR, Kamini SV. Floating effervescent tablet: A Review.Journal of Pharmaceutical and Biomedical Sciences 5, 2011.

24.     Pranjal KS, Shukla VK, Easwari TS, Sanjoo KRC, Alok NS, Saurabh S. Formulation Development And Evaluation of Mucoadhesive Oral Dosage Form Containing Clarithromycin Using Different Mucoadhesive Polymers. International Journal of Pharmaceutical Science And Health Care 2, 2012, 159-171.

25.     Singh BN, Kim KH. Floating drug delivery systems an approach to oral controlled drug delivery via gastric retention, J Control Rel 63, 2000, 235-59.

26.     Sinko P.J, Martin’s Physical Pharmacy and Pharmaceutical Sciences.Published by WoltersKlwner Health Pvt. Ltd, New Delhi 5, 2007, 553-559.

27.     The United States Pharmacopeial Convention. Stage 6 Harmonization Official December 1,2012, 616.

28.     Shah SH, Patel JK, and Patel NB, stomach specific floating drug delivery system: A review. International Journal of Pharmatech Research, 2009 ; July-September.

29.     Sharma S, PrasharM,Sahu R.  Floating drug delivery system: Incredible revolution . Pharmacology online .2011 , 3, 1039-1054.

30.     Talukder R, Fissihi R. Gastroretentive Delivery System: A MINI Review. Drug Dev. and Ind. Pharm.2004, 30, 1019-1028.

31.     Panchan HA, Tiwari AK. A Novel Approach of Bilayer Tablet Technology: A Review. International Reasher Journal of Pharmacy.2012 , 3, 44-49.

32.     Pujar ND, Gokani RK, Paun JS. Bilayer Tablet-An Emerging Trend. International Journal of Pharmaceutical Research and Development . 2012, 4, 102-111.

 

 

 

 

Received on 10.12.2015          Accepted on 01.01.2016        

© Asian Pharma Press All Right Reserved

Asian J. Res. Pharm. Sci. 6(1): Jan.-Mar., 2016; Page 37-44

DOI: 10.5958/2231-5659.2016.00006.0