Formulation, Development and In-vitro Evaluation of Alendronate Buccal Tablets

 

Iswarya Obilineni1, Srikala Kamireddy2, A V S Ravi Sai Nadh1, Supriya Chatla3,

Vadivelan Ramachandran4, Kanuri Bhuvaneswari5, Padavala Harika5

1Assistant Professors, KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada

2Assistant Professor, Nirmala College of Pharmacy, Atmakur, Guntur

3Associate Professor, Nirmala College of Pharmacy, Atmakur, Guntur

4Professor, Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, Nilgris, Tamil Nadu, India.

5B. Pharmacy Students, KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada

*Corresponding Author E-mail: aishwarya.111188@gmail.com, aishwaryauday4@gmail.com

 

ABSTRACT:

The aim of this work was to develop Alendronate mucoadhesive buccal tablets. Buccal tablets of Alendronate are designed to release drug at mucosal site for extended period of time without wash out of drug by saliva. Sodium alginate, Ethyl cellulose and Carbopol were selected as mucoadhesive polymers on the basis of their matrix forming properties. The objective of the study is to improve the bioavailability of Alendronate buccal tablets. In present study, an attempt was made to design mucoadhesive buccal tablets containing Alendronate, Sodium alginate, Ethyl cellulose and Carbopol using as polymers. The tablets were prepared by direct compression method. The formulations were evaluated for hardness, thickness, friability, weight variation, drug content estimation, surface pH determination, swelling index, in vitro drug release. The obtained results of various evaluation parameters are described in post compression studies. The results of in vitro release study were in full support of swelling study. In vitro release data of optimized formula F11 fitted into various release kinetic models to study the release mechanism. All the prepared tablets were stable at different temperature and shows good mucoadhesive properties.

 

KEYWORDS: Alendronate, Buccal drug delivery system, Mucoadhesive, direct compression method, polymers

 

 


INTRODUCTION: 

Osteoporosis is a disease characterised by decreased bone mass which leads to increased bone fragility1. The causes may be low BMI, post menopausal status, low calcium intake, cigarette smoking, alcohol abuse etc.

 

Alendronate is the drug belongs to the class of Bisphosphonates3 which is extensively used for the treatment of osteoporosis4. The administration of this drug involves side effects like gastrointestinal adverse events and oesophageal disorders5.

 

Eventhough various formulations of this drug were made with waxy coatings to protect the oesophagus, the risk is not completely erased6. Sustained release dosage forms provide a better control of plasma drug levels, less dosage frequency, less side effect, increased efficacy and constant delivery.7 One strategy to avoid GI toxicity is to deliver drugs systemically via intranasal, buccal or transdermal routes8.

 

The novel design of an oral controlled drug delivery system should primarily be aimed at a achieving more predictable and increased bioavailability of drugs9. Sustained release dosage forms provide a better control of plasma drug levels, less dosage frequency, less side effect, increased efficacy and constant delivery10. This novel drug delivery system promotes the ease and convenience of administration, deliverance of accurate dose as well as to prolong residence time of drug in contact with mucosa11. The most controlled drug delivery systems presently on the market embrace matrices, pellets, floating systems, liposomes, micro emulsions, liquid crystals, solid dispersions, Nano suspensions and percutaneous systems.12 Oral route is the most common route of drug delivery13. Within the oral cavity, buccal mucosa offers adorable route of administration14. Mucoadhesion can be defined as the ability of a synthetic or biological material to adhere (stick) to mucosa or mucus for an extended period of time15. For Mucoadhesion to occur, first an intimate contact must exist between the mucoadhesive polymer and the mucosa16. Mucoadhesive are synthetic or natural polymers, that will interact with the mucus layer which is present in the body at buccal cavity, and gastric mucosal layers17.

 

An ideal drug delivery system should deliver the drug in required amounts at intended time and desired rate18 where single dose or less frequent dosing for the whole duration of treatment and the dosage form must release active drug directly at the site of action19. The interest on the use of bioadhesive polymers has been increasing to control the delivery of biologically active agents and these agents has more advantages when compared to traditional routes20. Mucoadhesion, or the attachment of a natural or synthetic polymer to a biological substrate, is a practical method of drug immobilization or localization and an important new aspect of controlled drug delivery21. Buccal drug delivery system became an attractive site for the delivery of drugs as it is easy to administer the drugs through this route22. Buccal drug delivery system is defined as the administration of drug through buccal mucosa where the drug directly enters in to systemic circulation through jugular veins23,24. Bucoadhesive drug delivery system utilizes the property of adhesion of certain polymers25. Buccal tablets are designed to release the drug by targeting buccal mucosa or in to the saliva26.

 

The drugs taken through this route has much bioavailability as they bypass the gastrointestinal tract and hepatic portal system27. Buccal mucosa is most preferable than sublingual mucosa for sustained release formulations as the buccal mucosa is less permeable28. This route has increased ease of administration and is not associated with pain which increases the patient’s compliance29. The drug through this route can be administered even in unconscious patients30.

 

MATERIALS AND METHODS:

Alendronate (chandra labs), hydroxyl propyl methyl cellulose, sodium alginate, magnesium stearate (Rolex lab, Mumbai), micro crystalline cellulose, guar gum, ethyl cellulose,talc,aspartame (Fine chem laboratories)

Tablet compression machine-16 station (cadmach machinery co. pvt. ltd.), electronic balance (shimadzu), pH meter (elicopvt ltd),vernier calipers (pico India ltd), Erwekahardness tester (pharma test), Erwekafribilator (thermo lab), UV spectrophotometer (elicopvtltd, india), FT-IR (thermoelectron corporation (nicoletir 200), dissolution apparatus (lab indiausp xxii).

 

Formulation of mucoadhesive tablets of alendronate:

Preparation:

Inthiswork, direct compression method has been used to prepare buccal tablets with various polymers as the dry granulation and wet granulation methods increase the hardness of tablets.

 

Procedure31

All the ingredients were accurately weighed and were passed throughmesh no:60. Allthe ingredients were mixed thoroughly by blending geometrically inmortar and pestle for 10minutes then magnesium stearate and talc were mixed for 1-2min. Thepowder in various proportions were evaluated forf actors like angle of repose, Carr’s compressibility index and compressedinto tablets of diameter 9mm on Cadmach press 16 Station machine.

 

Characterization of tablets:

Thickness: The thickness was measured by using vernier calipersand  is expressed in mm.

 

Hardness: Tablets require a certain hardness and resistance to friability in order to withstand the mechanical shocks during the process of manufacturing, packing and shipping. Tablet’s hardness was measured by using Monsanto hardness tester.

 

Weight variation test: Ten tablets were selected and weighed individually to check for weight variation.

 

Friability: Hardness and friability of each ten randomly, selected tablets of each formulation using Erweka hardness tester (TBH30) and the Erweka friabilitor (GmbH,Germany) respectively.

 

Determination of Drug content: Twenty tablets were taken and triturated well. The quantity equivalent to 100mg of Alendronate was dissolved in 100ml of phosphate buffer pH 6.8 solutions on rotary shaker overnight. The solution was centrifuged and supernatant was collected.

 

Microenvironment pH study: The microenvironment pH of the tablets was determined by using the method which was proposed by Bottenberg, et al, 1991.The tablets were allowed to swell for 2 hours in 2ml of phosphate buffer (pH 6.8+0.05) in fabricated glass tubes and microenvironment pH was measured by placing the pH electrode in contact with the surface of the tablet and allowing it to equilibrate for 1minute.

 

Swelling Index: The swelling properties of the tablets were evaluated by observing the percentage of swelling. Each tablet was weighed (W1) and placed in petridish with 5ml of PB and incubated at 370C for predetermined times. After placing the formulation for specified time, the tablets were wiped off and weighed (W2).

 

Determination of the Ex Vivo Residence Time: It was found using a modified USP disintegration apparatus. The disintegration medium was composed of 800ml pH 6.8 phosphate buffer maintained at 37°C. The sheep buccal tissue was tied with thread to the central stand. The buccal tablet was hydrated with 0.5ml of pH 6.8 phosphate buffer and then the hydrated surface was brought in contact with the mucosal membrane. The time taken for complete erosion or dislodgment of the tablet from the mucosal surface was noted.

 

In vitro drug release study:

In vitro drug release study of mucoadhesive tablets were performed using standard USP dissolution apparatus type II (lab india USP XXII). The bowls of the dissolution apparatus was filled with 500ml of phosphate buffer pH 6.8 and maintained at a temperature of 37±0.50C. For each time interval, 5ml sample withdrawal and replacement of fresh media at predetermined time interval. The collected samples were filtered. The samples were analyzed for drug content using double beam UV spectrophotometer at 238nm.

 

RESULTS AND DISCUSSION:

Compatibility studies:

It can be utilized to quantify some components of an unknown mixture and can be used to analyze liquids, solids and gases. The FT-IR spectrum did not show presence of any additional peaks for new functional groups indicating no chemical interaction between drug and the used polymers.

 

 

Fig No. 1: FTIR Spectra of Alendronate Pure drug

 

Fig No. 2: FTIR Spectra of Alendronate sodium optimized formulation

 

Physical Evaluation of Bucoadhesive tablets:

All the tablets of different batches complied withthe official requirements of uniformity of weight as their weights varied between 297 and 310mg. The hardness of the tablets ranged from 4.0-4.4kg/cm2 and the friability values were less than 0.5% indicating that the Bucoadhesive tablets were compact and hard. The thickness of the tablets ranged from 3.70-3.78mm. All the formulations satisfied the content of the drug as they contained 98 to 101% of alendronate and good uniformity in drug content was observed.

 

Swelling Index:

The swelling index study indicated that the rate of swelling was directly proportional to Sodium alginate and polymer content. Swelling index was calculated with respect to time. The swelling index gives an indication of the relative moisture absorption capacities of polymers and whether the formulations maintain their integrity after moisture absorption.

 

Mucoadhesion time:

It was determined by using sheep buccal mucosa. This adhesion time relates to the release rate of drug. The bioadhesive tablet is important for good mucoadhesion.

 

In-vitro drug release study:

Table 1: In-vitro release of formulation F1-F6

Time

(hrs)

F1

F2

F3

F4

F5

F6

%DR

%DR

%DR

%DR

%DR

%DR

0

0

0

0

0

0

0

0.5

32.1

21.1

23.8

25.1

29.2

22.6

1

57.2

48.3

46.4

50.8

46.8

43.1

2

100.8

71.2

70.8

73.4

70.6

68.1

3

 

99.7

98.6

84.3

85.1

87.2

4

 

 

 

100.1

100.8

99.8

 

 

Fig 3: In-vitro drug release profiles of formulations F7 to F12

 

Table 2: In-vitro drug release study

Time

(hrs)

F7

F8

F9

F10

F11

F12

%DR

%DR

%DR

%DR

%DR

%DR

0

0

0

0

0

0

0

0.5

28.3

18.6

19.8

20.8

16.2

18.1

1

51.7

30.9

29.1

33.1

27.1

31.2

2

63.2

48.6

44.3

49.2

38.3

45.4

3

86.4

59.3

63.4

69.4

56.1

60.6

4

97.4

76.3

80.3

78.1

64.8

71.8

5

 

83.4

100.1

99.8

73.1

85.6

6

 

100.7

 

 

84.3

99.5

7

 

 

 

 

97.6

 

 

 

Fig 4: Dissolution graph for formulations F7-F12

 

The In-vitrodrug release study has been done for various formulations (F1-F12). The different ratios of polymers were used. The results shown that as the proportion of polymers in the formulation increases, cumulative percent drug released was found to be reduced.

 

CONCLUSION:

The mucoadhesive buccal tablets of Alendronate could be prepared using Ethyl cellulose and Carbopol by direct compression method. There was no drug-polymer and polymer-polymer interaction for the prepared muco adhesive buccal tablets observed from the results of FTIR study. All the prepared tablets were in acceptable range of weight variation, hardness, thickness, friability and drug content as per pharmacopoeia specifications. The surface pH of prepared buccal tablets was in the range of salivary pH, suggested that prepared tablets might be used without risk of mucosal irritation. The buccal tablets showed good swelling up to 4h in phosphate buffer pH 6.8 maintaining the integrity of formulation which is required for bio-adhesion.The prepared mucoadhesive buccal tablets of Alendronate were stable. Hence, the mucoadhesive buccal tablets of Alendronate can be prepared with enhanced bioavailability and prolonged therapeutic effect for the better management of hypercholesterolemic patients. The study conducted thus far reveals a promising result suggesting scope for pharmacodynamic and pharmacokinetic evaluation.

 

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Received on 09.02.2021             Modified on 21.12.2021

Accepted on 19.01.2023           © RJPT All right reserved

Research J. Pharm. and Tech 2024; 17(1):460-464.

DOI: 10.52711/0974-360X.2024.00072