Buccal Tablets of Lisinopril by Direct ... - Scientific Journals

A. Padole et al / Intl. R. J. of Pharmaceuticals (2012), Vol. 02, Issue 02, pp. 30-38

ISSN 2048-4143

Research Paper

Buccal Tablets of Lisinopril by Direct Compression Method for Buccal Drug Delivery Prasanth Vasantha Viswanadhan1, Anand Padole*1, Abin Abraham1 and Sam Thomarayil Mathew 2 1

Assistant Professor, Department of Pharmaceutics, Gautham College of Pharmacy, Sultanpalya, R.T. Nagar, Bangalore560032, Karnataka, India 2 Research Scholar, Department of Pharmaceutics, Gautham College of Pharmacy, Sultanpalya, R.T. Nagar, Bangalore560032, Karnataka, India 3 Accenture Pharmaceutical Services, Bangalore-560 072, Karnataka, India E-Mail: [email protected]

Abstract Buccal tablets of lisinopril were prepared by direct compression method using different hydrophilic polymers such as hydroxypropyl methylcellulose, sodiumcarboxy methylcellulose and Carbopol. All the prepared formulations showed satisfactory mass uniformity, thickness and favourable drug content. The friability of all the formulation was below 1%, which is an indication of good mechanical resistance of tablets. Among all the formulations, F4 showed maximum swelling index and in vitro release. Drug release mechanism was determined by plotting release data to Higuchi and KorsmeyerPeppas model. All the formulations are best fitted to Higuchi model and according to this model the drug releases from theses tablets may be controlled by diffusion. The surface pH of all formulations was found to be almost in neutral pH and no mucosal irritation was expected. The accelerated stability studies indicated that, the selected formulation (F4) showed almost same drug content, mass uniformity and residence time. No colour change or no any changes in texture were observed when tablets were tested in simulated saliva solution (pH 6.8). Keywords: Buccal Drug Delivery, Higuchi and Korsmeyer-Peppas Model, Stability Studies, In Vitro Release

1. Introduction Among the various transmucosal routes, buccal mucosa has excellent accessibility, an expanse of smooth muscle and relatively immobile mucosa, hence suitable for administration of retentive dosage form. Direct access to the systemic circulation through the internal jugular vein bypasses drugs from the hepatic first pass metabolism leading to high bioavailability (Navneet and Pronobesh, 2011). It had been a great challenge to the pharmaceutical sciences in order to enhance localised drug delivery or to deliver ‘difficult’ molecules (proteins and oligonucleotides) into the systemic circulation. Mucoadhesive systems remain in close contact with the absorption tissue, the mucous membrane releasing the drug at the action site leading to increase in bioavailability

(Amit et al, 2011). The area is well suited for a retentive device and appears to be acceptable to the patient. With the right dosage form design and formulation, the permeability and the local environment of the mucosa can be controlled and manipulated in order to accommodate drug permeation. Buccal drug delivery is a promising area for continued research with the aim of systemic delivery of orally inefficient drugs as well as a feasible and attractive alternative for non-invasive delivery of potent peptide and protein drug molecules. However, the need for safe and effective buccal permeation absorption enhancers is a crucial component for a prospective future in the area of

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buccal drug delivery (Shivam and Jain, 2011). Technically, an ideal buccal adhesive system must have the following properties: (1) maintains its position in the mouth for a few hours, (2) releases the drug in a controlled fashion, and (3) provides drug release in a unidirectional way toward the mucosa (Kashappa et al, 2004). Various buccal adhesive dosage forms, such as discs, microspheres, and bilayered tablets, have been thoroughly prepared and reported by several research groups. Limited studies, however, exist on novel devices that are superior to those of conventional buccal adhesive systems for the delivery of therapeutic agents through buccal mucosa (Kashappa et al, 2004). Mucoadhesive polymers have been utilised in many different dosage forms in efforts to achieve systemic delivery of drugs through the different mucosa. These dosage forms include tablets, patches, tapes, films, semisolids and powders (Patel et al, 2011). Lisinopril is an ACE inhibitor used in the treatment of hypertension. Lisinopril is slowly and incompletely absorbed following oral administration. Its oral bioavailability is about 25% only (Beermann et al, 1988). The aim of the present study was to develop mucoadhesive buccal tablets of Lisinopril to improve bioavailability and also to ensure satisfactory drug release.

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mixed ingredients. Ethyl cellulose was used as backing layer to prevent the bidirectional flow (Vijaya et al, 2010). 2.2.2. Evaluations 2.2.2.1. Weight Variation, Hardness and Thickness Twenty tablets were randomly selected from each batch and individually weighed using digital balance (Citizon, Model No. CG 203). Hardness was measured using Monsanto hardness tester and the thickness was measured by using digital vernier calliper (International Biological Laboratories). 2.2.2.2. Friability Ten tablets were weighed (Wo) and placed in the Roche friabilator and was rotated at 25 rpm for 4 minutes. After revolutions, the tablets were dedusted and weighed again (W). The percentage friability was measured using the following formula. Percentage friability = 1- (W/Wo) ×100 Where, Wo = Initial weight of tablet W = Weight of tablets after revolution

2. Materials and Methods

2.2.2.3. Content Uniformity

2.1. Materials

Ten tablets from each formulation were taken, crushed and mixed thoroughly. From the mixture, quantity of mixture equivalent of 5 mg lisinopril, was extracted with 50 mL methanol and filtered through Whatmann No.1 filter paper. The amount of drug present was determined using UV spectrometer (Shimadzu 1800, Japan) at 210 nm.

Lisinopril was obtained as a gift sample from Lincoln Pharmaceutical Ahmedabad, India. Hydroxypropyl methylcellulose (HPMC K-4M), sodium carboxy methylcellulose (Na CMC) and Carbopol 934-P was obtained from Sigma Chemicals, USA. Aspartame was obtained from Strides Arco Labs, Bangalore, India. Mannitol, magnesium stereate and ethyl cellulose were supplied from Loba Chemie Mumbai, India. 2.2. Methods 2.2.1. Preparation of Buccal Tablets of Lisinopril Mucoadhesive buccal tablets containing Lisinopril were prepared by direct compression method. The ingredients of the core layer (Table 1) were weighed accurately and mixed by trituration in a glass mortar and pestle for 15 minutes. All the ingredients were screened through sieve no. 100. The above mixture was then compressed using 6 mm punch on 10 stages rotary tablet compression machine (Riddhi Pharma Machinery Ltd, Model No. RDB4 -10, Ahmedabad, India). In order to obtain constant tablet weight the mannitol was added as filler excipient in the core layer. After compression of tablets, the upper punch was removed carefully without disturbing the set up and

2.2.2.4. Swelling Studies For conducting the swelling study, the tablet was weighed (Wo) and placed in a petri dish containing 5 mL of phosphate buffer (pH 6.8) for 8 hours. After that, the tablets were taken out from the petri dish and excess water was removed carefully by using filter paper and weighed again (Wt). The swelling index was calculated using the following formula (Ashok et al, 2011).

SI = (Wt-Wo) / Wo × 100 Where SI = Swelling index. Wt = Weight of tablets after time (t) Wo = Weight of tablet before placing in the Petri dish

2.2.2.5. Surface pH Study The tablet is allowed to swell by keeping it in contact with 1 mL of phosphate buffer (pH 6.8) for 2 hours at room


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temperature. The pH is identified by bringing the electrode into contact with the tablet surface and allowing to equilibrating for 1 minute (Prashant et al, 2011). The experiment was repeated thrice and data.

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(Nakamura et al, 1996 and Gazzi et al, 2009). The disintegration medium was composed of 800 mL (pH 6.8) of phosphate buffer maintained at 37 °C. The pig buccal mucosa was tied to the surface of a glass slab, vertically attached to the disintegration apparatus. The buccal tablet

Table 1. Composition of Lisinopril Buccal Tablets

Formulation Code Compositions F1

F2

F3

F4

F5

F6

F7

F8

5

5

5

5

5

5

5

5

Carbopol 934P (mg)

12.5

16.7

25

33.3

12.5

16.7

25

33.3

HPMC K4M (mg)

37.5

33.3

25

16.7

-

-

-

-

Na CMC (mg)

-

-

-

-

37.5

33.3

25

16.7

Mannitol (mg)

42

42

42

42

42

42

42

42

Magnesium stearate (mg)

2

2

2

2

2

2

2

2

Aspartame (mg)

1

1

1

1

1

1

1

1

Ethyl cellulose (mg)

20

20

20

20

20

20

20

20

Lisinopril (mg)

2.2.2.6. Bioadhesive Strength Bioadhesive strength of tablets was measured using modified physical balance. In the present study, pig mucosa was used as the mucosal membrane. The mucosal membrane was separated by removing the underlying fat and loose tissues. The membrane was washed with distilled water and then with phosphate buffer (pH 6.8) at room temperature. The tablet was placed in the lower part of the glass bottle and the buccal mucosa was allowed to adhere to the tablet and the glass bottle was tightly fitted to a inverted glass beaker which was kept in a 250 mL beaker (filled with phosphate buffer pH 6.8). The entire set up was kept in the left pan. Then the water was added drop wise to the empty plastic glass which was kept in the right pan (Vaidya et al, 2009) as shown in Figure 1. From the mucoadhesive strength, force of adhesion and then the averages of three determinations were calculated. Force of adhesion (N) = (Bioadhesive strength/100) × 9.81 Where as 9.81 is acceleration due to gravity (m/sec2)

2.2.2.7. Residence Time The ex vivo residence time was determined using a locally modified USP disintegration (Electrolab ED-2L) apparatus

was hydrated using phosphate buffer (pH 6.8) and the hydrated surface was brought in contact with the mucosal membrane. The glass slide allowed to move up and down, so that the tablet was completely immersed in the buffer solution at the lowest point and was out at the highest point as shown in Figure 2. The time taken for complete displacement of the tablet from the mucosal surface was noted and repeated thrice. 2.2.2.8. In Vitro Dissolution The drug released from the buccal tablets of lisinopril was studied using the USP II dissolution (Electrolab, TDT08L) test apparatus (Manivannan et al, 2008). The dissolution medium was 200 mL of phosphate buffer (pH 6.8) maintained at 37 ± 1 ºC and stirred at 50rpm. The tablet was fixed onto the glass disk with the help of cyanoacrylate adhesive. The disk was put at the bottom of the dissolution vessel so that the tablet remained on the upper side of the disk as shown in Figure 5. Samples (2 mL) were withdrawn at predetermined time intervals (1, 2 3, 4, 5, 6, 7 and 8 h), and replaced with an equal volume same dissolution medium. The samples were filtered through 0.45-µm filter (Millipore) and assayed spectrophotometrically at 215 nm. The mechanism of drug release from the buccal tablets was determined by Higuchi and Korsmeyer-Peppas plots (Higuchi, 1961; Korsmeyer et


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Figure 1. Determination of Bioadhesive Strength of Lisinopril Buccal Tablet

al, 1983 and Prasanth et al, 2011). 2.2.2.9. Stability Studies of Selected Lisinopril Buccal Tablet (F4) Selected lisinopril buccal tablets were packed in an aluminium foil and stored in an amber coloured glass bottles. These bottles were subjected to accelerated stability testing using stability chambers maintained at 40 ± 0.5 ºC and 75 ± 5% RH (Relative Humidity) for six months. Stability of selected lisinopril buccal tablet was carried out in simulated saliva solution (pH 6.8) and examined for changes in weight variation, residence time.

3. Results and Discussion 3.1. Weight Variation Hardness Thickness, Friability and Drug Content The physico-chemical characteristics of the lisinopril buccal tablets are shown in Table 2. All the formulation showed almost uniform mass, thickness and showed favourable drug content between 98.23 and 100.65%. The weight of the tablets was varied between 118.1 ± 1.33 and to 120 ± 2.18 mg and thickness ranged between 4.44 ± 0.05 and 4.54 ± 0.04 mm. The hardness and friability lies between 6.9 ± 0.19 and 7.18 ± 0.15 Kg/cm2, and 0.34 ± 0.15 and 0.47 ± 0.05 % respectively. In all the formulation, friability fallen below 1%, which is an indication of good mechanical resistance of tablets. 3.2. Swelling Studies The swelling index of mucoadhesive tablets are shown in Table 3 and Figure 3. It is manifest that an increase in the amount of Carbopol-934P causes increases in swelling index along with the decreasing amount of hydroxypropyl

methylcellulose K-4M and sodium carboxy methylcellulose (see Table 1). Among all the formulations, F4 showed maximum swelling index of 235.3 after 8th and followed by, F3, F2, F19, F8, F7, F6 and F5. Even if the swelling indices were high, the formulations maintained their integrity during the study period. From the swelling index results (as given in Table 3), it was concluded that swelling increases as the time proceeds because the polymer gradually absorb water due to hydrophilicity of polymer. The outermost hydrophilic polymer get hydrated which results in and swelling and a gel barrier is formed at the outer surface. As the gelatinous layer progressively dissolves and / or disperses. The swelling behaviour provides an idea regarding the moisture intake capacities of polymers and the differences in swelling of the hydrophilic polymers, may be due to the difference in resistance of the matrix network structure. 3.3. Surface pH The surface pH was determined in order to investigate the possibility of any side effects, in the oral cavity as acidic or alkaline pH is bound to cause irritation to the buccal mucosa. Surface pH of all formulations was found to be almost in neutral pH and ranged between 6.2 and 7.1 and no mucosal irritation was expected. The surface pH of all the formulations is shown in Table 4. 3.4. Bioadhesive Strength and Residence Time The bioadhesion strength and residence time of lisinopril buccal tablets are shown in Table 5 & Figure 4. Adhesion occurs shortly after the beginning of swelling but the bond formed between mucosal layer and polymer is not very strong. The adhesion will increase with the degree of hydration until a point where over-hydration leads to an abrupt drop in adhesive strength due to disentanglement at the polymer/tissue interface. The formulation F4 showed


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Figure 2. Determination of Residence Time of Lisinopril Buccal Tablet

Table 2. Physico-Chemical Characteristics of The Lisinopril Buccal Tablets

Formulation Code

Weight Variation (mg)*

Hardeness (Kg/cm2)**

Thickness (mm)***

Friability (%) ***

Drug Content (%) ***

F1

120 ± 2.18

7.18 ± 0.15

4.49 ± 0.06

0.39 ± 0.05

98.69 ± 0.21

F2

118.1 ± 1.33

6.98 ± 0.18

4.44 ± 0.05

0.34 ± 0.15

98.23 ± 0.10

F3

120.15 ± 2.08

7 ± 0.16

4.48 ± 0.06

0.41 ± 0.08

99.77 ± 0.35

F4

118.4 ± 2.14

6.9 ±0.19

4.54 ± 0.04

0.44 ± 0.13

100.28 ± 0.79

F5

120.15 ± 1.09

7.08 ± 0.29

4.47 ± 0.01

0.42 ± 0.08

99.67 ± 0.19

F6

118.3 ± 1.45

7.16 ± 0.15

4.52 ± 0.03

0.34 ± 0.22

98.58 ± 0.15

F7

119 ± 1.52

7.04 ± 0.23

4.45 ± 0.02

0.36 ± 0.05

99.79 ± 0.07

F8

119.4 ± 2.14

7.16 ± 0.15

4.49 ± 0.02

0.47 ± 0.05

100.65 ± 0.40

*Mean ± SD, n = 20, **Mean ± SD, n = 5, ***Mean ± SD, n = 10

maximum mucoadhesion strength and residence time. The mucoadhesive strength of the formulation F4 was found to be maximum of 1.15 Newton . This may be due to fact that positive charges on surface of Carbopol 934-P, could give rise to strong electrostatic interaction with mucous or negatively charged mucous membrane. The residence time of buccal tablets ranged between 7-11 hour and noted this much time required for buccal tablets to detach from the buccal mucosa. 3.5. In Vitro Dissolution In vitro release of lisinopril buccal tablets is shown in Figure 5. The formulations F4 showed a maximum release

of 98.12% after 8 hours. Similarly it shows maximum swelling index as well. It is apparent that the higher release of lisinopril occurred from the tablets contain higher proportion of Carbopol 934P. Initially in dry state lisinopril is distributed uniformly throughout the polymer matrix. After coming in contact with dissolution and as gelation takes place the release of lisinopril occurs from the surface of the swollen matrix. The movement of lisinopril to the surface is governed by the viscosity of the external hydrogel phase. Also Carbopol in its nonneutralized form does not become gel completely, as it still remain in coiled form. As the proportion of Carbopol increases, viscosity also decreases in the same order. Thus, a higher release with larger proportion of Carbopol may be


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Figure 3. The Swelling Index of Lisinopril Buccal Tablets Table 3. The Swelling Index of Lisinopril Buccal Tablets

Formulation code

Time (hr)

F1

F2

F3

F4

F5

F6

F7

F8

0

0

0

0

0

0

0

0

0

0.5

46.0

40.7

45.3

50.3

11.3

16.3

17.7

18.7

1

73.0

77.7

71.7

79.7

24.7

29.3

38.7

42.3

2

112.3

113.3

104.7

132.3

62.0

68.3

68.3

79.0

3

130.7

148.3

138.3

152.7

68.3

74.3

84.7

94.7

4

141.0

156.7

155.0

192.0

90.0

95.3

103.3

107.0

5

152.3

170.3

175.0

205.7

101.3

106.0

115.0

125.0

6

165.3

171.7

194.0

208.7

127.3

130.0

135.3

135.7

7

171.0

183.0

205.3

215.0

138.3

149.3

151.3

155.7

8

184.0

190.0

213.7

225.7

162.7

171.7

176.7

181.7

Table 4. Surface pH of Buccal Tablets

Table 5. In vitro Residence Time and Bioadhesive Strength of Lisinopril Buccal Tablets

Formulation Code

Surface pH

Formulation Code

Residence Time (Hours)*

Bioadhesive Strength (N)*

F1 F2 F3 F4 F5 F6 F7 F8

7.1 6.8 6.4 6.2 7.0 6.8 6.5 6.2

F1 F2 F3 F4 F5 F6 F7 F8

8.21± 0.19 8.43±0.09 9.54±0.59 10.68±0.37 7.18±0.12 7.51±0.05 8.65±0.40 9.45±0.13

0.70±0.008 0.88±0.010 1.02±0.006 1.15±0.017 0.69±0.017 0.73±0.040 0.82±0.015 0.93±0.021

Mean ± SD, n = 3

* Mean ± SD, n =


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Table 6. The r2, ‘k’ and ‘n’ Values of Lisinopril Buccal Tablets

Formulations F1 F2 F3 F4 F5 F6 F7 F8

Higuchi r2 0.9867 0.984 0.9949 0.9945 0.9801 0.983 0.9955 0.9906

Kosmeyer-Peppas r2 n 0.5394 1.2375 0.4991 1.2283 0.516 1.2964 0.5195 1.3168 0.5537 1.2708 0.4962 1.234 0.5126 1.2824 0.5001 1.2954

k ˃1 ˃1 ˃1 ˃1 ˃1 ˃1 ˃1 ˃1

Mechanism of Drug Release Predominantly Higuchi Predominantly Higuchi Predominantly Higuchi Predominantly Higuchi Predominantly Higuchi Predominantly Higuchi Predominantly Higuchi Predominantly Higuchi

Table 7. Stability Studies of Selected Lisinopril Buccal Tablet

1st Month

2nd Month

3rd Month

4th Month

5th Month

6th Month

Weight Variation (mg)*

117.3 ± 1.11

117.0 ± 1.02

116.1 ± 2.10

115.2 ± 1.11

115.0 ± 0.98

115.0 ± 1.0

Residence Time (Hours)**

10.2 ± 0.52

10.0 ± 0.81

9.9 ± 0.45

9.6 ± 0.32

9.6 ± 1.2

9.5 ± 0.99

Drug Content (%) ***

99.99 ± 0.12

99.52 ± 0.22

98.99 ± 0.42

98.20 ± 0.12

98.1 ± 0.89

98.00 ± 1.20

Evaluation Parameter

*Mean ± SD, n = 20, **Mean ± SD, n = 3, ***Mean ± SD, n = 10

Figure 4. Bioadhesive Strength of Buccal Tablets a) Physical balance, b) Inverted empty bottle, c) Bottle Cap, d) Lisinopril Buccal Tablet e) Pig Buccal Mucosa


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observed. Drug release mechanism was determined by plotting release data to Higuchi and Korsmeyer-Peppas model. All the formulations are best fitted to Higuchi model, according to this model the drug releases from theses tablets may be controlled by diffusion through the micropores. The r2,‘k’ and ‘n’ values are shown in Table 6. 3.6. Stability Studies Stability studies of lisinopril buccal tablets of F4, are shown in Table 7. During the end of accelerated stability study of selected formulation (F4) shows almost same drug content as observed in beginning of the study and also shows satisfactory uniform in weight and residence time. No colour change or no any changes in texture were observed when tablets were tested in simulated saliva solution (pH 6.8).

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is not suitable in designing mucoadhesive tablets and a combination of Carbopol with other polymers produces tablets with neutral pH that are safe for mucosal membrane. The swelling behaviour of Carbopol is high in all the formulation wherever Carbopol is used as more quantity and showed maximum release of lisinopril from the prepared lisinopril buccal tablet. The release studies indicated that the prepared lisinopril buccal tablets improved the bioavailabity by avoiding the first pass metabolism. Novel mucoadhesive buccal tablets of lisinopril were developed to overcome the first-pass metabolism and subsequent low bioavailability of the lisinopril. The in vitro studies have shown that this is a potential drug delivery system for lisinopril with a considerably good stability and release profile.

References Amit, A., Ajazuddin, D.K.T., Tekeshwar, V.S., Jyoti, M., and Sandip, P. (2011) Mechanism responsible for mucoadhesion of mucoadhesive drug delivery system A Review. International Journal of Applied Biology and Pharmaceutical Technology, 2, pp. 434-445. Ashok, T., Ganesh, K.G., Manasa, B., Subaldebnath, C., Santosh, K., and Chiranjib, B. (2011) Design and evaluation of controlled release mucoadhesive buccal tablets of candesartan. Journal of Pharmaceutics and Cosmetology, 1, pp. 125-130. Beermann, B. (1988) Pharmacokinetics of lisinopril. The American Journal of Medicine, 85(3), pp. 25-30. Gazzi, S., Chegonda, K.K., Chandra, S.R.G., Vijaya, K.B., and Prabhakar, R.V. (2009) Formulation and evaluation of bioadhesive buccal drug delivery of tizanidine hydrochloride tablets. AAPS Pharm. Sci. Tech., 10, pp. 530-539.

Figure 5. In vitro Release of Lisinopril Buccal Tablets

Higuchi, T. (1961) Rate of release of medicaments from ointment bases containing drugs in suspension. J. Pharm. Sci., 50, pp. 874-875.

4. Conclusion Buccal tablets of lisinopril were prepared using different hydrophilic polymers such as hydroxypropyl methylcellulose, sodiumcarboxy methylcellulose and Carbopol in different ratios and combinations, to study the effect of these polymers on the physio chemical characters, swelling index and in vitro drug release of lisinopril from the lisinopril buccal tablets. Initially we have prepared all the formulations by altering the polymer quantity randomly and from these formulations eight formulations (i.e. F1, F2, F3, F4, F5, F6, F7 and F8) were selected as best formulations for further studies. Among all the eight formulations, F4 showed maximum swelling index, bioadhesive strength, residence time and in vitro drug release also. The surface pH indicates that Carbopol alone

Kashappa, G.H.D., and Pramod, K.T.M. (2004) Preparation and evaluation of a novel buccal adhesive system. AAPS Pharm. Sci. Tech., 5, pp. 1-9. Korsmeyer, R.W., Gurny, R., Doelker, E., Buri, P., and Peppas, N.A. (1983) Mechanism of potassium chloride release from compressed, hydrophilic, polymeric matrices: effect of entrapped air. J. Pharm. Sci., 72, pp. 1189-1191. Manivannan, R., Balasubramaniam, A., Prem Anand, D.C., Sandeep, G., and Rajkumar, N. (2008) Formulation and in vitro evaluation of mucoadhesive buccal tablets of diltiazem hydrochloride. Research J. Pharm. and Tech., 1, pp. 478-480.


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Nakamura, F., Ohta, R., Machida, Y., and Nagai, T. (1996) In vitro and in vivo nasal mucoadhesion of water soluble polymers. Int. J. Pharm., 134, pp. 173-181. Navneet, V., and Pronobesh, C. (2011) Polymeric Platform for mucoadhesive buccal drug delivery system A Review. Int. J. Curr. Pharm. Res., 3, pp. 3-8. Patel, K.V., Patel, N.D., Dodiya, H.D., and Shelat, P.K. (2011) Buccal bioadhesive drug delivery system An overview. International Journal of Pharmaceutical & Biological Archives, 2, pp. 600-609. Prasanth, V.V., Puratchikody, A., Sam, T.M., and Ashok, K.B. (2011) Development and characterization of eudragit based mucoadhesive buccal patches of salbutamol sulphate. Saudi Pharmaceutical Journal, 19, pp. 207214. Prashant, A.B., Taware, G.V., Hariprasanna, R.C., and Najmuddin, M. (2011) Development and evaluation of mucoadhesive buccal tablets of loratadine. Journal of Pharmacy Research, 4, pp. 2699-2702. Shivam, T., and Jain, N. (2011) Buccal control drug delivery system A Review. International Journal of Pharmaceutical Science and Research, 2, pp. 13-24. Vaidya, V.M., Manwar, J.V., Mahajan, N.M., and Sakarkar. D.M. (2009) Design and in vitro evaluation of mucoadhesive buccal tablets of terbutaline sulphate. Int. J. Pharm. Tech. Res., 1, pp. 588-597. Vijaya, K.S., Stephen, R.B., and Ganesh, S.B. (2010) Preformulation study of buccoadhesive monolayered tablets of carvedilol. International Journal of Pharma and Bio Sciences [Internet], pp. 1-10. Available from: [Accessed 13 July 2011].


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