INTRODUCTION:

The oral mucosa offers a preferable route for both local and systemic delivery of drugs. This delivery route extends numerous advantages over the other delivery routes such as oral, parenteral and dermal, due to its rich blood supply, rapid onset of action, avoidance of the first pass metabolism as well as enzymatic degradation, which results in enhanced bioavailability, increased patientcompliance, and easy of self-medication.buccal disintegrating formulation specially for geriatric and pediatric patient and gives grate patient complies.they can easily dissolve or disintegrate in saliva. Buccal drug delivery is a favourable route compare to parenteral, injectable and adds a several advantages over other routes. The parenteral route offers excellent bioavailability, similarly having poor patient compliance, anaphylaxis, and some other infections.

Fig.No. 1: Schematic representation of the different linings of mucosa in mouth

Buccal and sublingual route of drug delivery are most generally within which local and systemic effects are treated. The permeability of oral mucosa denotes the physical nature the tissues. The permeable part is sublingual mucosa and buccal mucosa is thinner part and within which there's a high blood flow and surface area; it's a feasible site when a rapid onset of action is desired.

OBJECTIVE:

1. To Improve Bioavailability.

2. To Increase Prolong Release Action And Specific Site Of Action Of Dosage Form.

3. To Increase Patient Compliance .

4. To Increase Safety, Efficacy And Mechanism Of Action Of Dosage Form.

5. To Increase Solubility Of BCS Class 2 Drug By Using Superdisintegrant And Surfactant

RATIONAL STUDY:

The solubility most significant parameter they depends on action of medication, so poor solubility BCS class 2 drug by using superdisintegrants agent and ready of immediate release dosage form and buccal disintegrant dosage form increase the solubility and offers a much better mode of action of medication. they're going to be increase therapeutic efficacy furthermore as bioavailability of medication.

Generally the standard dosage form are administered by oral routes, but mostly various category drug undergone hepatic first pass metabolism there for fewer amount of drug reached in to circulation .Therefore Buccal drug delivery system is one among the most effective alternative first pass metabolism.

Calibration curve of gabapentin ²⁴:

Table No.1

Sample No.	Concentration (μg/ml)	Absorbance at 210 nm
1.	0	0
2.	0.2	0.061
3.	0.4	0.124
4.	0.6	0.183
5.	0.8	0.245
6.	1	0.306

Figure No.2- Calibration curve of Gabapentin with 6.8 pH buffer at 210 nm

FTIR Studies ²⁵

Identification of drug and drug-polymer compatibility study Procedure

The FTIR spectra of the pure drug, excipient and physical mixture of drug and excipient were recorded in between 400-4000 frequency (cm-1). No peaks are observed which interfere with the most drug peaks. the subsequent spectrum and table shows IR spectrum for drug and polymer and also the frequency of characteristic bands for the identical.

The IR Spectrum preview pictures are as follows:

Figure.No.3: I.R. Spectrum of Gabapentin

Figure.No.4: I.R. Spectrum of Gabapentin with polymers

Identification of Gabapentin with polymers I.R. Spectrum

Table No.2

Sr. No.	Wave Number(cm-1)	Functional group
1.	3473	N-H
2.	2362	O-H
3.	2915	C-H
4.	1669	C=O
5.	1102	C-N
6.	1362	C-O

Experimental Work:

Preformulation Studies:

1. Organoleptic Charecters²⁶

2. Solibility Study ²⁷

3. Melting Point ²⁸

4. Micrometric Properties of Drug ²⁹

4.1. bulk density:

4.2 tapped density:

4.3 compressibility index:

4.4 hausner’s ratio:

4.5 angle of repose:

Formulation of Buccal Disintegrating Gabapentin Tablets ^30,31

The key process in the formulation development of Gabapentin. Tablets including direct compression method to be adopted using different superdisintegrant and before weighing active ingredient. The dispensing area maintained temperature below 25ºC and humidity below 30 % RH.

Procedure:

Accurately weigh the active (Gabapentin) and every one other ingredients, were individually knowledgeable sieve no.44 then all the ingredients were mixed thoroughly by triturating upto 15 min. The mixed powder was lubricated with talc and also the powder was again mixed thoroughly for punching to tablets by Direct compression method. All the formulations were prepared in keeping with direct compression method were prepared as per the procedure given below and aim is to Buccal Disintegrating tablet of Gabapentin.

Table No.3 Composition of Buccal disintegrating tablet:

Sr. no.	Ingredients (mg/tablet)	F1	F2	F3	F4	F5	F6	F7	F8	F9
1.	Gabapentin	10	10	10	10	10	10	10	10	10
2.	Cross povidone	4	5	7.5	-	-	-	-	-	-
3.	Cross carmalose	-	-	-	4	5	7.5	-	-	-
4.	Sodium starch glycolate	-	-	-	-	-	-	4	5	7.5
5.	PVP K 30	5	5	5	5	5	5	5	5	5
6.	MCC	250	248	246	250	248	246	250	248	246
7.	Sucrose	230	230	230	230	230	230	230	230	230
8.	Talc	0.6	0.6	0.6	0.6	0.6	0.6	0.6	0.6	0.6
9.	Mg. sterate	1	1	1	1	1	1	1	1	1
10.	Peppermint oil	q.s.	q.s.	q.s.	q.s.	q.s.	q.s.	q.s.	q.s.	q.s.

RESULT ANDDISCUSSION

1. Micrometric properties of drug

Table No. 4

Formulation Code	Bulk Density (g/cm³⁾	Tapped Density (g/cm³⁾	Carr’s Index (%)	Hausner Ratio (%)	Angle of Repose (θ)
F1	0.298	0.377	13.63	1.26	15.64
F2	0.294	0.370	11.76	1.25	14.57
F3	0.307	0.373	12.12	1.21	15.10
F4	0.312	0.357	10.76	1.14	15.10
F5	0.312	0.350	15.15	1.12	15.64
F6	0.307	0.363	16.41	1.18	15.10
F7	0.296	0.357	12.12	1.20	15.10
F8	0.305	0.338	17.64	1.10	14.57
F9	0.303	0.344	13.4	1.13	15.10

2. Physical Evaluation of formulated tablets

Table No. 5

Formulation Code	Weight Variation (mg)	Thickness (MM)	Hardness (kg/cm²)	Friability (%)	Content uniformity (%)	Disintegration test (sec/min)	Swelling studies (%)
F1	498	6.7	5.7	0.69	98.12	56	56.23
F2	503	6.5	5.9	0.56	98.58	1.10	53.23
F3	508	6.1	6	0.66	97.02	58	53.22
F4	503	6.7	5.5	0.59	99.13	39	48.49
F5	505	6.8	5.3	0.62	99.33	42	42.56
F6	500	6.6	5.6	0.58	99.01	51	48.45
F7	511	6.7	5.1	0.55	97.25	1.20	45.23
F8	491	6.5	5.2	0.53	97.98	1.09	44.52
F9	510	6.6	5.3	0.50	98.91	1.11	42.23

3. In-vitro release study

Table No. 6

Formulation code/ Time (min)	F1	F2	F3	F4	F5	F6	F7	F8	F9
0	0	0	0	0	0	0	0	0	0
3	42.21%	38.52%	52.32%	21.79%	42.89%	51.12%	38.95%	22.62%	25.91%
6	62%	58.66%	59.32%	48.98%	55.93%	56.32%	43.23%	29.31%	55.11%
9	89.21%	78.01%	63.08%	69.51%	69.38%	63.23%	66.21%	62.25%	67.14%
12	91.21%	85.02%	84.56%	85.14%	98.63%	91.23%	76.56%	69.21%	79.27%
15	94.33%	87.00%	89.21%	91.25%	99.99%	96.96%	87.59%	93.20%	81.25%
18	94.33%	91.32%	95.39%	96.52%	99.99%	98.97%	91.26%	93.20%	91.03%
21	97.00%	96.54%	97.28%	98.23%	99.99%	98.85%	95.36%	96.31%	95.30%

Fig. No. 5 Comparative study of In-vitro% drug release curve of formulation F1, F5 and F8.

CONCLUSION:

From the above observation in vitro drug release graph shows the upper drug release formulation is F1, F5 and F8. after comparative study perform between F1,F5 and F8 formulation we conclude F5 formulation is higher drug release it gives 99.99% release. And performed In Vitro Permeation of Drug study from graphical observation found to be F5 formulation gives excellent 95.19% drug diffuse through membrane. The angle of repose values of formulation is 15.64 θ which is superb. Bulk and tapped densities are used for the measurement of compressibility index. the majority density is 0.312 g/cm3 and tapped density is 0.350 g/cm3.The compressibility index value is 15.15 % Of the formulation F5 and it's good flow respectively. The hausner’s ratio values is 1.12 which is Free flowing. F5 formulation showed good results the full Gabapentin drug release was about 99.33 % indicating almost the whole drug release from the formulation of F5 with the cross carmalose. It having the disintegration time 42 sec. they gives confirmation F5 formulation we can be used as to Buccal drug delivery system.the present research conclude Buccal disintegrating tablet is most acceptable and accurate Buccal dosage form which bypass hepatic system and shows more therapeutic response.the pharmaceutical companies prefer dosage form due to both patient compliance (especially paediatric and geriatric) as well as industrial acceptability. This technology is a good tool for product life cycle management for increasing patient life of existing product.

REFERENCE:

1. Rameshwari S, Jeya Anandhi J Arulmigu Kalasalingam College Of Pharmacy, Tamilnadu Asian Journal Of Pharmaceutical And Clinical Research July-September 2009; 2(3). Issn 0974-2441.

2. Gandhi SD, Pandya PR, Umbarkar R, Tambawala T And Shah Ma. Mucoadhesive Drug Delivery System- An Unusual Maneuver For Sitespecific Drug Delivery System, Inter. J. Pharm. Sci., 2011, 851- 872.

3. K. Naga Raju, S. Velmurgan, B. Deepika, Sundar Vinushitha, Klr Pharmacy College, Poloncha, Andhra Pradesh, International Journal Of Pharmacyand Pharmaceutical Science, Volume 3,2011, Page No. 239-246.

4. Elnay JC, Swarbick J, Boylan JC. Encyclopedia Of Pharmaceutical Technology. 2nd Ed. New York: Marcel Dekkar.1990;189.

5. N. S. Miller, M. Chittchang, T. P. Johnston. The Use Of Mucoadhesive Polymers In Buccal Drug Delivery. Adv Drug Delivery Review. 2005; 57:1666- 91.

6. N. K. Jain. Controlled And Novel Drug Delivery. 1st Ed. Cbs Publishers, New Delhi, 2002.

7. Chowdary KPR, Srinivas L. Mucoadhesive Drug Delivery Systems: A Review of Current Status. Indian Drugs 2000; 37(9): 400-06.

8. Khanna R, Agarwal SP, Ahuja A. Mucoadhesive Buccal Drug Delivery: A Potential Alternative to Conventional Therapy. Indian Journal Of Pharmaceutical Science 1998;60 (L):1-11.

9. Squier CA., Kremer MJ., Biology of Oral Mucosa and Esophagus. J. Natl Cancer Inst. Monogr. 2001, 29: 7–15.

10. Senel S, Kremer M, Nagy K, Squier C. Delivery of Bioactive Peptides and Proteins Across Oral (Buccal) Mucosa. Curr Pharm Biotechnol 2001; 2:175-86.

11. Khairnar GA, Sayyad FJ. Development Of Buccal Drug Delivery System Based on Mucoadhesive Polymers. International Journal of Pharmtech Research. 2010; 2(1): 719-735.

12. Khairnar GA, Sayyad FJ. Development of Buccal Drug Delivery System Based on Mucoadhesive Polymers. International Journal of Pharmtech Research. 2010; 2(1): 719-735.

13. Wani MS. Current Status in Buccal Drug Delivery [Online]. [Cited 2007 Nov 15]; [11screens]. Available from: Url: Www.Pharmainfo.Net.

14. Ghaly ES, Ruiz G. Mucoadhesive Delivery Systems Using Carrageenan and Eudragit RL [Online]. [Cited 2006 Aug 6]; [9 Screens]. Available From: Url: Www. Aaps Pharm Sci Tech.

15. Senel S, Kremer M, Nagy K, Squier C. Delivery of Bioactive Peptides and Proteins Across Oral (Buccal) Mucosa. Curr Pharm Biotechnol 2001; 2:175-86.

16. Gandhi RB., Robinson JR., Oral Cavity as A Site for Bioadhesivedrug Delivery. Adv. Drug Deliv. Rev. 1994, 13: 43–74.

17. Gama-Scintigraphy. Int. J. Pharm. 1987, 40, 119–123 39.

18. Smart JD., Lectin-Mediated Drug Delivery in The Oral Cavity. Adv. Drug Deliv. Rev. 2004, 56: 481–489.

19. Madhusudan RY, Vani G, Rameshachary Br. Design and Evalution Of Mucoadhesive Drug Delivery System. Indian Drug. 1998; 35(9): 134-141.

20. Roy S, Pal K, Anis A, Prabhakar B. Polymer In Mucoadhesive Drug Delivery System: A Brief Note. Design Monomers and Polymers. 2009; 12:483-95.

21. Johnson JB, Davis DA, Davies F. Gray’s Anatomy. 32nd Ed. London (England): Longmans Green and Co; 1958. P.737.

22. Squier CA, Nany D. Buccal Drug Delivery System. Arch Oral Biol 1985; 30: 313-18.

23. Varma S, Kaul M, Rawat A, Siani S. An Overview on Buccal Drug Delivery System. International Journal of Pharmaceutical Science and Research. 2011;2(6): 1303-1321.

24. Pimlott SJ, Addy M. Site Dependent Absorption Study on Buccal Mucosae. Oral Surg Oral Med Oral Pathol Oral RadiolEndod 1985; 59:145-48.

25. Hearnden V, Sanker V, Hull K, Jural DV, Greenberg M, Kerr RA, Lockhart PA. New Developments and Opportunities in Oral Mucosal Drug Delivery for Local and Systemic Disease. Advance Drug Delivery Reviews. 2011; 1-13.

26. Shraddha R Nagpure, Prerana B Jadhav. Formulation Development and Evaluation of Gabapentin Buccal Tablets International Journal of Innovative Pharmaceutical Sciences and Research 2018, 6 (06), 13-22 Issn (Online) 2347-2154.

27. Http://Drugbank.Ca/Drugs/Db00996(Aprd00015)

28. K. Govindasamy. Formulation and Evaluation of Gabapentin Oral Controlled Release Matrix Tablets Submitted to The Tamil Nadu Dr. M.G.R. Medical UniversityChennai – 32 In The Department Of Pharmaceutics Reg. No: 26106811, Page No.54.

29. K. Govindasamy. Formulation and Evaluation of Gabapentin Oral Controlled Release Matrix Tablets Submitted to The Tamil Nadu Dr. M.G.R. Medical UniversityChennai – 32 In The Department Of PharmaceuticsReg. No: 26106811, Page No.60.

30. K. Govindasamy. Formulation and Evaluation of Gabapentin Oral Controlled Release Matrix Tablets Submitted To The Tamil Nadu Dr. M.G.R. Medical UniversityChennai – 32 In The Department Of Pharmaceutics Reg. No: 26106811, Page No.52.

31. Timmermans J, Moes AJ. Factors Controlling The Buoyancy And Gastric Retentioncapabilities Of Floating Matrix Capsules. New Data For Reconsidering The Controversy. J. Pharm. Sci. 1994; 83: 18-24

32. Swetha. Koorapati. Formulation And In Vitro Evaluation of Gastroretentive Dosage Form Of Gabapentin. Submitted To The Tamil Nadu Dr. M.G.R. Medical University, Chennai Reg.No:26103014, Page No. 110

33. Kenneth E. Avis, Herbert A. Lieberman, And Leon Lachman. Pharmaceutical Dosage Forms, Tablets, 3 Rd Edition, Published By: Marcel Dekker, Vol-1, 42- 56.

34. Waldwell, L.J; Gardner. C.R; Cargil, R. C; Us Patent 4, 1988; 735,804.

35. Doddayya Hiremath Et AL. Formulation and Evaluation of Controlled Release Matrix Tablets Of Ambroxol Hydrochloride. Journal Of Pharmacy Research. 2010; 3(8),1810-1813.

36. Robinson JR. Sustained and Controlled Release Drug Delivery System, 2nd Edition, Published By: Marcel Dekker, 138-171.

37. Srikrishna T., K. Mohammad Anees Design, Development and Evaluation of Buccal Tablets of Pregabalin Emerging Trends in Multidisciplinary Research Volume No. 10. Issue No. 2 Issn Print 0974-3618, 2017

38. Robinson JR. Sustained and Controlled Release Drug Delivery System, 2nd Edition, Published By: Marcel Dekker, 138-171.

39. Gilbert S Banker, Modern Pharmaceutics, 4th Edition, Published By: Marcel Dekker; 297-321.

40. Timmermans J, Moes AJ. The Cut Off Size for Gastric Emptying of Dosage Forms. J.Pharm. Sci. 1993; 82: 854.

Received on 24.02.2022 Modified on 27.03.2022

Asian J. Res. Pharm. Sci. 2022; 12(2):123-127.

DOI: 10.52711/2231-5659.2022.00020