Formulation and
Evaluation of Bioadhesive Buccal Drug Delivery of Sumatriptan Succinate Tablets
Dr. Y. Krishna Reddy, Juveria
Tasleem
Department of Pharmaceutics,
Nalanda College of Pharmacy, Jawaharlal Nehru Technological University,
Hyderabad, Telangana.
*Corresponding Author E-mail: rajinisuralabs1@gmail.com
ABSTRACT:
The objective of
this study was to develop effective buccal tablets of Sumatriptan Succinate.
Tablets of Sumatriptan Succinate were prepared by direct compression method
using bioadhesive polymers like Poloxamer188, β‐CD, HPMC K4M. Buccal tablets
were prepared by taking polymers in different ratios. The formulation F9 showed
maximum drug release (98.92%) in 8 hrs. It was considered as optimized
formulation.
KEYWORDS: Sumatriptan
Succinate, Buccal tablets, Poloxamer188, β‐CD, HPMC K4M, in-vitro
drug release.
INTRODUCTION:
Among the various routes of
drug delivery, oral route is the most suitable and most widely accepted one by
the patients for the delivery of the therapeutically active drugs. But after
oral drug administration many drugs are subjected to presystemic clearance in
liver, which often leads to a lack of correlation between membrane
permeability, absorption and bioavailability.(1-5) Within the oral
route, the Buccal cavity is an attractive site for drug delivery due to ease of
administration and avoids possible drug degradation in the gastrointesinal
tract as well as first pass hepatic metabolism.(6)
Buccal Delivery involves the
administration of drug through buccal mucosal membrane (the lining in the oral
cavity). The drug directly reaches to the systemic circulation through the
internal jugular vein and bypasses the drugs from the hepatic first pass
metabolism, which leads to high bioavailability.(7)
A suitable buccal drug
delivery system should be flexible and should posses good bioadhesive
properties, so that it can be retained in the oral cavity for the desired
duration. Bioadhesive formulations have been developed to enhance the
bioavailability(8,9) of drugs that undergo substantial first pass
hepatic effect and to control the drug release to a constant rate.(10) In
addition ,it should release the drug in a controlled and predictable manner to
elicit the required therapeutic response.(11-13) Various buccal
mucosal dosage forms are suggested for oral delivery which includes: buccal
tablets, buccal Patches and buccal gels.(14,15)
MATERIALS:
Sumatriptan Succinate was
Provided by SURA LABS, Dilsukhnagar, Hyderabad. Poloxamer188, β‐CD, HPMC K4M, MCC, PVP K30, Mg
Stearate, Talc was gift samples from Sd fine Chem.Ltd. Mumbai, India.
METHADOLOGY:
Formulation development of
tablets:
Buccal tablets were prepared
by a direct compression method, before going to direct compression all the
ingredients were screened through sieve no.100. Poloxamer188, β‐CD and HPMC K4M are the
mucoadhesive and biodegradable polymers used in this preparation of buccal
mucoadhesive drug delivery systems.
Sumatriptan Succinate was
mixed manually with different ratios of Poloxamer188, β‐CD and HPMC K4M and
Microcrystalline Cellulose as diluent for 10 min. The blend was mixed with talc
and magnesium stearate for 3-5 min.
Table No:1 Formulation Chart
|
INGREDIENTS |
FORMULATION CHART |
|||||||||||
|
F1 |
F2 |
F3 |
F4 |
F5 |
F6 |
F7 |
F8 |
F9 |
F10 |
F11 |
F12 |
|
|
Sumatriptan Succinate |
25 |
25 |
25 |
25 |
25 |
25 |
25 |
25 |
25 |
25 |
25 |
25 |
|
Poloxamer188 |
15 |
30 |
45 |
60 |
- |
- |
- |
- |
- |
- |
- |
- |
|
β‐CD |
- |
- |
- |
- |
15 |
30 |
45 |
60 |
- |
- |
- |
- |
|
HPMC K4M |
- |
- |
- |
- |
- |
- |
- |
- |
15 |
30 |
45 |
60 |
|
MCC |
150 |
135 |
120 |
105 |
150 |
135 |
120 |
105 |
150 |
135 |
120 |
105 |
|
PVP K30 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
Mg stearate |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
|
Talc |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
|
Total Weight |
200 |
200 |
200 |
200 |
200 |
200 |
200 |
200 |
200 |
200 |
200 |
200 |
4. Evaluation of
Pre-Compression Blend:
They were evaluated for their
characteristic parameter such as Tapped density, Bulk density, Carr’s index,
Angle of repose, Hausner’s ratio.
Preparation of Tablets:
Then the powder blend was
compressed into tablets by the direct compression method using 7mm flat faced
punches. The tablets were compressed using a sixteen station LAB PRESS rotary
tablet-punching machine.
EVALUATION OF BUCCAL TABLETS:
Physicochemical
characterization of tablets:
The prepared Sumatriptan
Succinate buccal tablets were studied for their physicochemical properties like
weight variation, hardness, thickness, friability and drug content as Per IP
Procedures.
In vitro release studies:
The dissolution medium was
500ml of pH 6.8 phosphate buffer at 50rpm at a temperature of 37 ± 0.5°C.
Samples of 5ml were collected at different time intervals up to 8 hrs and
analyzed after appropriate dilution by using UV Spectrophotometer at 229nm.
Kinetic Analysis of
Dissolution Data:
To analyze the in vitro
release data various kinetic models were used to describe the release kinetics.
1.
Zero – order kinetic model – Cumulative % drug released versus time.
2.
First – order kinetic model – Log cumulative percent drug remaining
versus time.
3.
Higuchi’s model – Cumulative percent drug released versus square root
of time.
4.
Korsmeyer equation/Peppa’s model– Log cumulative % drug released versus
log time.
Surface pH:
Weighed tablets were placed in
boiling tubes and allowed to swell in contact with pH 6.8 phosphate buffer
(12mL). Thereafter, surface pH measurements at predetermined intervals of 0.25,
0.5, 1, 2, 3, 4, 5, 6, 7, and 8 h were recorded with the aid of a digital pH
meter.
Moisture absorption:
Agar (5% m/V) was dissolved in
hot water. It was transferred into Petri dishes and allowed to solidify. Six
buccal tablets from each formulation were placed in a vacuum oven overnight
prior to the study to remove moisture. They were then placed on the surface of
the agar and incubated at 37°C for one hour.
Final
weight – Initial weight
% Moisture Absorption =
------------------------------------ x 100
Initial weight
RESULTS AND DISCUSSION:
Evaluation:
Characterization of
pre-compression blend:
The pre-compression blend of
Sumatriptan Succinate buccal tablets were characterized with respect to Angle
of repose was less than 25.83o, carr’s index values were less than
15.1 for the pre-compression blend of all the batches indicating good to fair
flowability and compressibility. Hausner’s ratio was less than 1.25 for all the
batches indicating good flow properties.
Table No:2 Physical properties
of pre-compression blend
|
Formulation Code |
Angle of repose (Ө) |
Bulk density (gm/cm3) |
Tapped density (gm/cm3) |
Carr's Index (%) |
Hausner's ratio |
|
F1 |
25.83 ±0.0094 |
0.57 ± 0.99 |
0.68 ± 0.54 |
15.1 |
1.25 ± 0.12 |
|
F2 |
24.64 ±0.0087 |
0.51 ± 0.89 |
0.62 ± 0.68 |
14.6 |
1.24 ± 0.32 |
|
F3 |
22.32 ±0.0039 |
0.52 ± 0.72 |
0.66 ± 0.74 |
13.3 |
1.21 ± 0.42 |
|
F4 |
22.61 ±0.0041 |
0.56 ± 0.53 |
0.61 ± 0.87 |
12.3 |
1.22 ± 0.56 |
|
F5 |
20.76 ±0.0058 |
0.52 ± 0.64 |
0.62 ± 0.91 |
14.7 |
1.21 ± 0.57 |
|
F6 |
20.89 ±0.0049 |
0.51 ± 0.97 |
0.67 ± 0.21 |
14.6 |
1.24 ± 0.48 |
|
F7 |
20.72 ±0.0056 |
0.53 ± 0.78 |
0.64 ± 0.32 |
13.4 |
1.23 ± 0.43 |
|
F8 |
20.82 ±0.0041 |
0.50 ± 0.84 |
0.64 ± 0.45 |
12.3 |
1.22 ± 0.59 |
|
F9 |
20.69 ±0.0074 |
0.54 ± 0.54 |
0.63 ± 0.51 |
14.1 |
1.24 ± 0.39 |
|
F10 |
22.35 ±0.0063 |
0.56 ± 0.41 |
0.64 ± 0.65 |
14.5 |
1.23 ± 0.45 |
|
F11 |
19.65 ±0.0055 |
0.54 ± 0.31 |
0.62 ± 0.781 |
13.1 |
1.22 ± 0.67 |
|
F12 |
23.45 ±0.0002 |
0.55 ± 0.12 |
0.65 ± 0.89 |
12.2 |
1.21 ±0.87 |
Evaluation of buccal tablets:
Physical evaluation of
Sumatriptan Succinate buccal tablets: All the physical attributes
of the prepared tablets were found to be practically within control limits.
Table No:3 Physical evaluation
of Sumatriptan Succinate buccal tablets
|
Formulation code |
Average Weight (mg) |
Thickness (mm) |
Hardness (Kg/cm2) |
Friability (%) |
Content uniformity (%) |
|
F1 |
198.62 |
3.21 |
4.2 |
0.16 |
98.62 |
|
F2 |
200.17 |
3.56 |
4.9 |
0.53 |
99.12 |
|
F3 |
197.12 |
3.11 |
4.1 |
0.47 |
97.25 |
|
F4 |
199.84 |
3.52 |
4.5 |
0.64 |
98.34 |
|
F5 |
196.54 |
3.45 |
4.8 |
0.72 |
96.29 |
|
F6 |
199.23 |
3.49 |
4.6 |
0.33 |
99.25 |
|
F7 |
197.49 |
3.62 |
4.0 |
0.42 |
97.68 |
|
F8 |
199.86 |
3.39 |
4.7 |
0.41 |
99.61 |
|
F9 |
197.42 |
3.48 |
4.6 |
0.62 |
98.10 |
|
F10 |
196.35 |
3.52 |
4.2 |
0.33 |
98.34 |
|
F11 |
199.81 |
3.86 |
4.8 |
0.51 |
99.34 |
|
F12 |
198.25 |
3.61 |
4.5 |
0.46 |
97.82 |
In vitro release studies:
Table No:4 In vitro
dissolution data for formulations F1 – F12 by using Poloxamer188 , β‐CD and HPMC K4M polymers.
|
Time (hrs) |
F1 |
F2 |
F3 |
F4 |
F5 |
F6 |
F7 |
F8 |
F9 |
F10 |
F11 |
F12 |
|
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
0.5 |
24.29 |
22.11 |
28.12 |
21.75 |
22.27 |
33.60 |
31.32 |
38.95 |
26.12 |
18.41 |
19.16 |
10.56 |
|
1 |
41.96 |
36.22 |
35.24 |
33.35 |
33.19 |
42.24 |
45.71 |
46.20 |
35.54 |
28.87 |
21.23 |
17.24 |
|
2 |
56.55 |
45.67 |
41.15 |
42.16 |
42.96 |
54.55 |
52.89 |
52.89 |
49.87 |
36.57 |
32.97 |
21.65 |
|
3 |
64.82 |
57.88 |
53.63 |
46.27 |
48.40 |
59.15 |
57.32 |
63.66 |
55.92 |
47.32 |
37.65 |
29.78 |
|
4 |
69.24 |
62.91 |
57.42 |
58.62 |
53.96 |
67.99 |
62.81 |
68 |
61.21 |
53.79 |
42.52 |
31.67 |
|
5 |
73.47 |
66.43 |
61.10 |
65.51 |
61.31 |
72.81 |
70.36 |
72.74 |
74.72 |
67.56 |
49.56 |
47.72 |
|
6 |
81.15 |
74.42 |
65.97 |
68.96 |
66.73 |
79.20 |
77.21 |
78.18 |
89.91 |
79.24 |
53.48 |
52.35 |
|
7 |
86.60 |
89.51 |
69.18 |
72.54 |
73.48 |
82.32 |
81.78 |
83.69 |
95.23 |
83.45 |
61.24 |
66.23 |
|
8 |
98.86 |
92.42 |
86.48 |
78.47 |
82.15 |
89.93 |
96.12 |
93.88 |
98.92 |
89.71 |
80.42 |
73.84 |
Fig No:1 In vitro dissolution
data for formulations F1 - F12 by using Poloxamer188, β‐CD and HPMC K4M polymers.
From the above graphs it was
evident that Poloxamer188 in the concentration of 10% of polymer of the total
tablet weight (F1) drug with other three ratios 20%, 30%, 40% Total polymer
tablet weight ratios. where as in F4 formulation the quantity of polymer was
because high hence it showed more drug retardation with less drug release that
is 78.47 % in 8 hrs.
From the above graphs it was
evident that β‐CD in the Polymer concentration of 30% of the total tablet(F7), is
showing better result 96.12 % drug release when compared with other three
ratios F5, F6, F8, As the concentration of polymer increases the retarding of
drug release also increased.
From the above graphs it was
evident that HPMC K4M in the Polymer concentration 10% of the total tablet
weight (F9), is showing better result 98.92% drug release when compared with
other three formulations. where as in F11, F12 formulations the concentration
become high and the drug release was retarded less.
Table No:5 moisture
absorption, surface pH, bioadhesion strength values of selected formulations.
·
In F5 Formulation Moisture Absorption is 53 And Surface Ph is 6.11.
·
In F9 Formulation Moisture Absorption is 62 And Surface Ph is 6.18.
·
In F10 Formulation Moisture Absorption is 49 And Surface Ph is 6.14.
6. Release kinetics:
The data was fitted into
various kinetic models such as zero, first order kinetics, higuchi and
korsmeyer peppas mechanisms and the results were shown in below table. This
formulation was following Higuchi release mechanism with regression value of
0.985.
Table No:5 Release kinetics and
correlation coefficients (R2)
|
Cumulative (%) Release Q |
Time (T) |
Root (T) |
Log (%) Release |
Log (T) |
Log (%) Remain |
Release rate (Cumulative % Release / t) |
1/Cum% Release |
Peppas log Q/100 |
% Drug Remaining |
|
0 |
0 |
0 |
|
|
2.000 |
|
|
|
100 |
|
26.12 |
0.5 |
0.707 |
1.417 |
-0.301 |
1.869 |
52.240 |
0.0383 |
-0.583 |
73.88 |
|
35.54 |
1 |
1.000 |
1.551 |
0.000 |
1.809 |
35.540 |
0.0281 |
-0.449 |
64.46 |
|
49.87 |
2 |
1.414 |
1.698 |
0.301 |
1.700 |
24.935 |
0.0201 |
-0.302 |
50.13 |
|
55.92 |
3 |
1.732 |
1.748 |
0.477 |
1.644 |
18.640 |
0.0179 |
-0.252 |
44.08 |
|
61.21 |
4 |
2.000 |
1.787 |
0.602 |
1.589 |
15.303 |
0.0163 |
-0.213 |
38.79 |
|
74.72 |
5 |
2.236 |
1.873 |
0.699 |
1.403 |
14.944 |
0.0134 |
-0.127 |
25.28 |
|
89.91 |
6 |
2.449 |
1.954 |
0.778 |
1.004 |
14.985 |
0.0111 |
-0.046 |
10.09 |
|
95.23 |
7 |
2.646 |
1.979 |
0.845 |
0.679 |
13.604 |
0.0105 |
-0.021 |
4.77 |
|
98.92 |
8 |
2.828 |
1.995 |
0.903 |
0.033 |
12.365 |
0.0101 |
-0.005 |
1.08 |
Fig No:2 Higuchi plot of
optimized formulation
FTIR:
There was no disappearance of
any characteristics peak in the FTIR spectrum of drug and the polymers used.
Fig No:3 FTIR Peak of Pure drug
Sumatriptan Succinate
Fig No:4 FTIR Peak of Optimised
formulation
АCKNOWLEDGEMENT:
Thе Authors arе
thankful to Sura Labs, Dilshukhnagar, Hydеrabad for providing thе
nеcеssary facilitiеs for thе rеsеarch work.
REFERENCES:
1.
K. Naga Raju, S. Velmurugan, B. Deepika, Sundar Vinushitha, Formulation
and In-vitro Evaluation of Buccal Tablets of Metoprolol Tartrate.International
Journal of Pharmacy and Pharmaceutical Sciences.2011; 3(2): 239-246.
2.
M.S. El-Samaligy, S.A. Yahia, E.B. Basalious, Formulation and
Evaluation of Diclofenac sodium buccoadhesive discs. International Journal of
Pharmaceutics.2004;286:27-39.
3.
Silvia Rossi, Givseppina Sandri, Carla M. Caramella, Buccal drug
delivery Today: Technologies.Drug Delivery or formulation and
nanotechnology.2005;2(1):59-65.
4.
Prasad B Kadam, Remeth J Dias, Kailas K Mali, Vijay D Havaldar,
Niranjan S Mahajan, Formulation and Evaluation of buccoadhesive tablets of
Atenolol.J Pharm Res.2008;1(2):193-199.
5.
Noha Adel Nafee, Fatma Ahmed Ismail, Nabila A Boraie, Mucoadhesive
Delivery Systems I, Evaluation of Mucoadhesive Polymers for Buccal Tablet
Formulation.Drug Dev Ind Pharm.2004;30(9):985-993.
6.
M.S. El Samaligy, N.N. Afifi, E.A. Mahmoud, Increasing Bioavailability
of silymarin using a buccal liposomal delivery system: Preparation and
Experimental design investigation. International Journal of
Pharmaceutics.2006;308:140-148.
7.
Choy Fun Wong, Kah Hey Yuen, Kok Khiang Peh., Formulation and
Evaluation of controlled release Eudragit buccal patches. International Journal
of pharmaceutics. 1999; 178:11-22.
8.
G. Ikinci, S. Senel, C.G. Wilson, Development of a buccal bioadhesive
nicotine tablet formulation for smoking cessation. International Journal of
Pharmaceutics. 2004; 27:173-198.
9.
N Lagoth, H Kahibacher, G Scoffmann, I Schmerold, M Schuh, Sonja franz,
Peter Kurka, Andreas Bernkop-Schnurch, Thiolated Chitosans: Design and In-vivo
Evaluation of a Mucoadhesive Buccal Peptide Drug Delivery
Systems.Pharmaceutical Research.2006;23(3):573-579.
10. Calum R
Park, Dale L. Munday, Development and Evaluation of a biphasic buccal adhesive
tablet for nicotine replacement therapy. International Journal of
Pharmaceutics.2002;237:215-226.
11. Yajaman Sudhakar,
Ketousetuo kuotsu, A.K. Bandyopadhyay, Buccal bioadhesive drug delivery-A
promising option for orally less efficient drugs. Journal of Controlled
Release.2006;114:15-40.
12. Han-Gon Choi,
Chong-Kook Kim, Development of omeprazole buccal adhesive tablet with stability
enhancement in human saliva. Journal of Controlled Release.2006; 68:397-404.
13. Gazzi Shaker,
Chegonda K. Kumar, Chandra Sekhara Rao Gonugunta, Formulation and Evaluation of
Bioadhesive Buccal Drug Delivery of Tizanidine Hydrochloride Tablets.AAPS
PharmSci Tech.2009; 10(2):530-539.
14. Noha A Nafee,
Fatma A Ismail, Mucoadhesive buccal patches of miconazole nitrate: in-vitro/
in-vivo performance and effect of aging. International Journal of
Pharmaceutics.2003; 264:1-14.
15. Vamshi Vishnu
Yamsani, Ramesh Gannu, Chandrasekhar Kolli, M.E. Bhanoji Rao and Madhusudhan
Rao Y. Development and in-vitro evaluation of buccoadhesive carvedilol tablets,
Acta Pharm.2007;57:185-197.
Received on 13.02.2020
Modified on 17.03.2020
Accepted on 10.04.2020 ©Asian Pharma Press All Right Reserved
Asian J. Pharm. Res. 2020; 10(2):105-109.
DOI: 10.5958/2231-5691.2020.00020.9