INTRODUCTION:

Sumatriptan is a selective serotonin agonist with good vasoconstrictor properties used in the treatment of migraine drug of triptan class. It is chemically known as 3-[2-(Dimethylamino) ethyl] –N-methyl-1H indole -5- methane sulphonamide succinate (1:1) base. Sumatriptan is rapidly but incompletely absorbed following oral administration and undergoes first pass metabolism resulting in a low absolute bioavailability of 14% with biological half life of 2.5 hours. It is official in British Pharmacopoeia^1-4.

Poly (lactide-co-glycolide) (PLGA):

L-lactide and DL-lactide have been used for copolymerization with glycolic acid monomers. Different ratios of poly (lactide-co-glycolide) have been commercially developed. Amorphous polymers are obtained for a 25L: 75G monomer ratio. A copolymer with a monomer ratio of 80L: 20G is semi-crystalline⁵. PLGA is the most commonly used FDA approved polymer⁶.

For many decades, medication of an acute disease or a chronic disease has been accomplished by delivering drugs to the patients via various pharmaceutical dosage forms like tablets, capsules, pills, creams, ointments, liquids, aerosols, injectables and suppositories as carriers⁷. Oral controlled release (CR) dosage forms (DFs) have been developed over the past three decades due to their considerable therapeutic advantages such as ease of administration, patient compliance and flexibility in formulation⁸. Microspheres can be described as small particles (1~1000µm) for use as carriers of drugs and other therapeutic agents⁹.

MATERIALS AND METHODS:

Sumatriptan Succinate Procured from Hetero Pharma limited Hyd, provided by Sura Pharma Labs, Dilsukhnagar, Hyderabad. PLGA, Methanol and Sodium lauryl sulphate procured from Merk specialiities Pvt Limited, Mumbai. Ethyl cellulose procured from M/S Micro labs limited, Hosur. India. HPMC K4M procured from Coloron Asia Private Limited; Goa. Dichloro methane procured from Qualikems Fine Chem Pvt., Ltd.

METHOD OF PREPARATION:

SOLVENT EVAPORATION METHOD:⁹

Sumatriptan Succinate microspheres were prepared using PLGA, Ethyl cellulose and HPMC K4M and distilled water as continuous phase by solvent evaporation technique. Initially dichloromethane (DCM) and methanol was mixed uniformly at room temperature, then PLGA, Ethyl cellulose and HPMC K4M in various proportions was dissolved in the above solution. To this mixture, a drug solution corresponding was added and mixed thoroughly and injected drop wise in to the continuous phase consisting of 100mL of 0.2% (w/v) SLS (sodium lauryl sulphate) at 250 rpm. The microspheres obtained was washed for 2-3 times with distilled water and dried at room temperature. Different concentrations and ratios of polymers used in the formulation of microspheres are mentioned in Table.

Table 1: Formulation chart of Sumatriptan Succinate Microspheres

Ingredients (MG)	Formulations
Ingredients (MG)	F1	F2	F3	F4	F5	F6	F7	F8	F9
Sumatriptan Succinate	25	25	25	25	25	25	25	25	25
PLGA	25	50	75	-	-	-	-	-	-
Ethyl cellulose	-	-	-	25	50	75	-	-	-
HPMC K4M	-	-	-	-	-	-	25	50	75
Dichloromethane (mL)	20	20	20	20	20	20	20	20	20
Methanol (mL)	30	30	30	30	30	30	30	30	30
Sodium lauryl sulphate (mg)	20	20	20	20	20	20	20	20	20

Characterization of Microspheres:

The microspheres were characterized by their micromeritic properties^10,11,18,19 such as Particle size, Bulk density, Tapped density, Compressibility index, Hausners ratio and Angle of repose. Percentage yield¹⁷, Drug entrapment efficiency¹², Swelling study, In vitro drug release study¹³, In Vitro drug release kinetics¹⁴,Fourier Transform Infrared (FTIR) spectroscopy^15,16,18,19.

RESULTS AND DISCUSSION:

Figure 1: Standard graph Of Sumatriptan Succinate in simulated gastric fluid pH 1.2

Figure 2: Standard graph Of Sumatriptan Succinate in pH 7.4 phosphate buffer

Evaluation and characterization of microspheres

Table 2: Micromeritic property of floating microspheres of Sumatriptan Succinate

Formulation code	Mean partical size	Bulk density ((gm./cm³))	Tapped density (gm./cm³)	Hauseners ratio	Carr’s index	Angle of repose
F1	412.14	0.434 ± 0.2	0.476 ± 0.3	1.095	8.695	23.2 ± 0.2
F2	421.95	0.277 ± 0.2	0.312 ± 0.2	1.133	11.11	25.2 ± 0.1
F3	458.41	0.588 ± 0.3	0.666 ± 0.4	1.333	11.76	27.1 ± 0.1
F4	410.15	0.521 ± 0.3	0.631 ± 0.3	1.121	17.39	24.4 ± 0.4
F5	420.96	0.625 ± 0.1	0.833 ± 0.1	1.333	25.00	28.3 ± 0.4
F6	441.65	0.476 ± 0.3	0.526 ± 0.2	1.105	9.52	25.1 ± 0.1
F7	425.14	0.416 ± 0.2	0.476 ± 0.3	1.142	12.50	26.7 ± 0.4
F8	432.69	0.384 ± 0.4	0.434 ± 0.3	1.130	11.53	26.0 ± 0.3
F9	461.54	0.555 ± 0.1	0.714 ± 0.1	1.285	22.22	26.6 ± 0.2

Table 3: Percentage yield and percentage drug entrapment efficiency of the prepared microspheres

S. No.	Formulation code	% yield	Drug Content (mg)	% Drug entrapment efficiency
1	F1	89.31	96.14	86.14
2	F2	91.12	98.65	90.91
3	F3	96.08	99.76	91.72
4	F4	90.74	98.14	95.58
5	F5	96.91	96.52	98.45
6	F6	98.24	100.04	93.87
7	F7	96.39	97.24	88.72
8	F8	98.52	98.53	92.51
9	F9	98.47	99.21	99.82

In vitro Mucoadhesion Test:

As the polymer to drug ratio increased, microspheres containing PLGA exhibited % mucoadhesion ranging from 61 to 70%, microspheres containing Ethyl cellulose exhibited % mucoadhesion ranging from 75 to 95% and microspheres containing HPMC K4M exhibited % mucoadhesion ranging from 78 to 93%. The results of In-vitro mucoadhesion test are compiled in Table 8.6. Effect of polymer proportion on % mucoadhesion is depicted in Figures 8.6 to 8.8 and comparative depiction of % mucoadhesion is depicted in Fig. Tab Percentage mucoadhesion of the prepared microspheres.

Table 4: In Vitro Mucoadhesion Test of all Formulations

S. No.	Formulation Code	No. of Microspheres		Percentage Mucoadhesion
S. No.	Formulation Code	Initial	Final	Percentage Mucoadhesion
1	F1	20	15.48	61
2	F2	20	11.85	58
3	F3	20	15.14	70
4	F4	20	17.96	93
5	F5	20	20.71	95
6	F6	20	16.17	75
7	F7	20	16.80	93
8	F8	20	11.58	86
9	F9	20	17.21	78

In-Vitro Drug Release Studies

Table 5: In-vitro drug release data of Sumatriptan Succinate microspheres

Time (H)	Cumulative percentage of drug release
Time (H)	F1	F2	F3	F4	F5	F6	F7	F8	F9
0	0	0	0	0	0	0	0	0	0
1	21.89	16.87	16.18	17.82	13.91	15.67	18.90	20.15	26.39
2	28.96	25.50	27.92	24.31	18.68	21.75	23.36	27.96	35.52
3	35.75	31.89	36.27	34.93	24.90	26.90	30.21	32.82	42.80
4	48.18	45.23	49.96	47.72	36.53	33.83	38.89	37.56	59.93
5	55.09	52.19	58.19	53.15	47.95	40.76	47.23	41.29	65.28
6	62.10	60.97	65.76	64.91	52.18	47.92	50.15	48.75	70.23
7	78.67	68.57	72.51	68.75	63.87	53.76	56.82	56.51	78.06
8	85.79	74.21	78.93	73.81	68.56	62.81	64.97	60.18	82.16
9	90.14	78.92	82.74	82.94	78.97	70.47	68.56	74.32	87.47
10	97.58	87.28	87.94	97.14	84.28	78.38	72.10	78.69	98.14
11		98.12	90.75		91.84	84.10	79.64	86.82
12			97.35		99.88	91.17	84.78	90.53

In vitro drug release from all the formulation was found to be slow and sustained over the period of 12 hours, among other formulation F5 showed better sustained release pattern and the cumulative percentage release at the end of 12 hours was found to be 99.88%.

Table 6: Release kinetics studies of the optimized formulation (F5)

Figure 3: Graph of zero order release kinetics of optimized formula

Optimised formulation F5 was kept for release kinetic studies. From the above graphs it was evident that the formulation F5 was followed zero order release kinetics.

FT-IR

FT-IR spectra of Pure drug

FT-IR spectra of optimised formulatio

Figure 4: FTIR graph

CONCLUSION:

Microspheres are prepared with PLGA, Ethyl cellulose and HPMC K4M successfully by the solvent evaporation technique. Microspheres of Sumatriptan Succinate showed excellent mucoadhesivity, % yield, Drug Content, % Drug entrapment efficiency and prolonged drug release up to 12 hours. Microspheres of different size and drug content could be obtained by varying the formulation variables. Thus the prepared microspheres may prove to be potential candidates for oral delivery devices. Formulation Batch F5 showed best appropriate balance between mucoadhesivity and drug release rate, which can be considered as a best fit for microspheres. The polymer ratio (Ethyl cellulose) of 1:2 were selected as best formulation, The formulated system showed sustained release up to 12 h and the system is potentially useful to overcome poor bioavailability problems associated with Sumatriptan Succinate . Analysis of drug release mechanism showed that the drug release from the formulations the best fit model was found to be zero order release kinetics. Hence it can be concluded that Sumatriptan Succinate loaded Ethyl cellulose Microsphere may be useful to achieve sustained drug release profile suitable for oral administration.

ACKNOWLEDGEMENT:

Thе Authors arе thankful to Principal, Department of Pharmacy, Samskruti College of Pharmacy, Hyderabad for extending the support to carry out the research work. Finally, the authors express their gratitude to the Sura Pharma Labs, Dilsukhnagar, Hyderabad, for providing research equipment and facilities.

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Received on 08.10.2022 Modified on 01.11.2022

Asian J. Pharm. Tech. 2023; 13(2):91-94.

DOI: 10.52711/2231-5713.2023.00017