INTRODUCTION:

Cefixime trihydrate (CT) is an orally active third-generation cephalosporin. Cephalosporins exhibit an extensive variety of functions towards gram-positive and gram-negative microorganisms; these are acted by restrain bacterial wall synthesis^1-3. Therefore, the remedy is essential with an agent, that has a broad spectrum of functions and is used within the therapy of simple UTI, acute and persistent bronchitis, pharyngitis, otitis media, and gonorrhea.

CT is poorly soluble in water precede its oral administration. It's far slowly and incompletely absorbed from the GIT, ensuing in only 40-50% bioavailability. Approximately 50% of absorbed drug is excreted in the urine in 24 hours and more than 10% of the administered dose is excreted via the bile. The elimination half-life of CT is 3 - 4 hours⁴. The objective of the present study is to determine the properties of polymers as an excipient that would form a gel-like matrix through formulations in tablets and control the release rate of the drug and which was expected to be mucoadhesive⁵.

The oral route is the most preferred and widely applicable route for the delivery of majority of the drugs. But the problems such as poor aqueous solubility, less residence time, chemical instability in the gastrointestinal tract minimize the bioavailability (BA) of orally administered drugs^6-9. Further, metabolism through various barriers or enzymes also degrades the drug before reaching site of action. Hence, various alternative drug delivery systems are developed to enhance the oral BA of these drugs¹⁰. The delivery systems include; enhancement of solubility through solid dispersions^11-12, liquisolid compacts¹³increase the stability and prolonged residence time through floating systems^14-16, lipid-based delivery systems for by passing metabolism with solid lipid nanoparticles, SMEDDS^17-20, transfersomes^21-22, nanostructured lipid carriers^23-24 and micronization for reducing particle size using nanosuspensions^25-26.

The mucoadhesive and bioadhesive polymers are hydrophilic and hydrophobic polymers, which are generally swellable nature networks, jointed by the number of cross-linking agents^27-28. These polymers are generally possessing optimum polarity to permit sufficient wetting by the mucus membrane and optimum fluidity that also permits the mutual adsorption capacity and interpenetration of the polymer and mucus to take place²⁹. Mucoadhesive polymers also used for the development of formulations for topical delivery, ocular delivery and brain delivery of drugs^30-33.

Chitosan is a cationic natural polysaccharide that's derived from the chitin of crustaceans, with crabs and shrimp-shell wastes as its predominant supply. Its peculiarities consist of a quantity of deacetylation and the common molecular weight of the polymer in addition to low toxicity and excellent bioavailability make it a novel excipient in pharmaceutical components as particularly new development. Together with chitin, chitosan is a good insight into the second one maximum plentiful polysaccharide subsequent to cellulose³⁴. These days there are such a lot of formulations that were developed and evaluated inside the dosage forms consisting of buccal, nasal, ophthalmic, sublingual, periodontal, transdermal, colon particular, vaginal, as well as gene carrier that is based on the utilization of chitosan and its derivatives³⁵. Microcrystalline chitosan (MCCh) is an especially crystalline grade of chitosan base can be particularly valuable as an excipient³⁶. The mucoadhesive tendency of chitosan may additionally rely upon its crystallinity. Efficient gel formation by way of MCCh may want to result in big mucoadhesion, at least as a long way as “adhesion through hydration” is concerned³⁷.

MATERIALS AND METHODS:

Cefixime Trihydrate was obtained as a gift sample from International health care limited, India. Hydroxy propyl methyl cellulose (HPMC K4M), guar gum (GG), and sodium carboxy methyl cellulose (Na-CMC), Guar gum, Chitosan, Lactose, Magnesium Stearate were obtained from Colorcon Asia Pvt. Ltd. and Loba chemicals, Mumbai.

Preparation of tablets:

In this research, the CT mucoadhesive tablets were prepared using the direct compression method using HPMC K4M, Na-CMC, and GG in different concentrations as rate controlling polymers. The drug CT and different degrees of deacetylated chitosan were powdered well in a mortar. The polymers were added little by little and blended manually to get a uniform fine powder mass. The final mass passed through a sieve (#80) to get uniform particles. To this final particles, add diluents like lactose, lastly, magnesium stearate, and talc were added to the final powder mass. Finally powder mass compressed into the tablets in a multiple punch Cadmach tablets machine. The formulations are shown in table 1.

Evaluation tests:

All the formulations were evaluated for hardness, weight variation, thickness, friability, drug content uniformity, assay, mucoadhesive strength and in-vitro dissolution study^38-40.

Tablet hardness test:

Hardness is the crushing strength of tablets which determines the ease of handling and rigors of transportation. For each formulation, 3 tablets were mainly used for this study. The hardness of separate tablets was determined and expressed in Kg/cm². The hardness tester is a Monsanto used⁴¹.

Weight variation test:

This test is conducted by weighing twenty tablets individually, calculating the average weights, and comparing the individual weight to the average⁴².

Table 1: Composition of Cefiximetrihydrate mucoadhesive tablets

Formulation (mg)	F1	F2	F3	F4	F5	F6	F7	F8	F9
Drug	200	200	200	200	200	200	200	200	200
HPMC K4M	75	100	125	-	-	-	-	-	-
Na-CMC	-	-	-	75	100	125	-	-	-
GG	-	-	-	-	-	-	75	100	125
Chitosan	25	25	25	25	25	25	25	25	25
Lactose	70	45	20	70	45	20	70	45	20
Talc	2.5	2.5	2.5	2.5	2.5	2.5	2.5	2.5	2.5
Magnesium Stearate	2.5	2.5	2.5	2.5	2.5	2.5	2.5	2.5	2.5

Thickness test:

It can be measured by using the Vernier caliper expressed in mm⁴³.

Friability test:

Friability tests are performed to access the effect of friction with shocks, which can often cause a tablet to break. Roche friabilator effect produced abrasions and shock generated utilizing round plastic chambers that revolves at 25rpm dropping tablets at a distance of 6inches with each revaluation. Pre weighed tablets were poured in the friabilator, this was then operated for 100 revolutions⁴⁴. Tablets were dedusted and re-weighed. The percent friability was noted using the below formula:

% F= (Wo-W) / Wo × 100,

Where

% F= Friability in percent;

Wo= Initial weight of tablet;

W= Weights of tablets after test

Assay:

For these 30 tablets can be randomly identified and select from all formulations. Out of 30 tablets, 10 were crushed into the fine powder. The powder taken equivalent to label claim was weighed accurately, dissolved in their respective media, and assayed individually at respective λ_max against its blank. The drug should be within 90 % to 110 % of its labeled claim⁴⁵.

Determination of mucoadhesive strength:

The effect of chitosan on mucoadhesive behavior of tablets was evaluated by the device which was mainly composed of a two-arm balance. The left balance was replaced by a small copper lamina plate vertically suspended through a wire. On the same side, a movable platform is maintained at the bottom to fix the model mucosal membrane^46-47.

Figure 1: Mucoadhesive apparatus

In-vitro dissolution studies:

The drug release effect of tablets depends on polymers such as HPMC, Na CMC, GG, and chitosan, the amount of polymers used, and other excipients in the tablets were studied by dissolution tests⁴⁸. In-vitro dissolution study carried using USP apparatus II type (Paddle Method) at 50 rpm. The dissolution test was carried out for a total period of 8 hr using buffer pH 6.8 solution (500ml) as dissolution medium at 37°C±1ºC 8 hr. 5ml sample can draw at periodic intervals viz 1-8 hour and it is makeup to 10mL with phosphate buffer 6.8 pH solution. 5mL of fresh medium was replaced and analyzed Spectrophotometrically at 285 nm^49-50.

Ex vivo mucoadhesion studies:

The effect of chitosan on mucoadhesive behavior of tablets were evaluated by the device described the same above was used with sheep intestinal mucosa as a model membrane. The mucosa lining was excised in pH 1.2 phosphate buffer before the bioadhesion evaluation study by removing the underlying connective and adipose tissue and equilibrated. The tablet that is lowered on to the mucosa under a constant weight of 5g for a total contact period of 1 min. Bioadhesive strength was assessed concerning the weight in grams required for the detachment of the tablet from the mucosa membrane. The experiment was performed in triplicate and the average value was calculated⁵¹.

Force of adhesion (N) = (muco-adhesive strength/100) ×9.8

Force of adhesion (N)

Bond strength (N/m2) = –––––––––––––––––––––––––––––––

Surface area of tablet (m2)

Kinetic analysis of dissolution data:

In the order of describing the kinetics of release the process of release drug in different type formulations, models were fitting to the dissolution data of optimized formulations using linear regression analysis^52-53.

Zero order release kinetics:

Qt= Qo-Kot

Q_t= amount of drug dissolved in time t,

Q_o= initial amount of drug

K_o=is zero order release rate constant

First order release kinetics:

The application of this model to drug dissolution studies used to describe the absorption and elimination of the drugs^54-55. With a first-order reaction, the amount of drug changes at a rate proportional to the amount of drug remaining. The first-order elimination rate is expressed as follows:

LogQt= logQo+K₁t/2.303

Q_t = amount of drug released time t,

Q_o= initial amount of drug

K₁ = is the first-order release rate constant

Higuchi model:

Many theoretical models were Higuchi developed and the study of drug release of water-soluble and low soluble drugs incorporated in semi-solid and/or solid matrixes⁵⁶. Mathematical expressions obtained for drug release particles were dispersed in the uniformed matrix system behaving as diffusion media, the equation is

Q_t = K_H.t½

Q_t = amount of drug released in the time t,

K_H = is Higuchi dissolution constant

Higuchi model explains the release as the diffusion process based on the Fickslaw, squareroot time dependent.

Korsemeyer and peppas model:

This model can be generally used to analyze the release of pharmaceutical polymeric dosage forms, when the release mechanism is not well known or when > one type of release phenomenon could be involved⁵⁷.

Mt/M = K.t_n

Mt/M -- the fraction amount drug release

n is the diffusion exponent for the release and it depends on that shape of the matrix dosage form. If n < 0.45, Fickian diffusion mediated drug release occurs⁵⁸. Non- Fickian release occurs if 0.45< n<0.89 and erosion⁵⁹ (i.e. complete matrix relaxation) mediated release occurs in n=0.89.

RESULTS AND DISCUSSIONS:

General properties:

All of the formulations batches of the tablets containing Cefixime.T were evaluated for their organoleptic properties which are odour, colour, and taste.

Shape and thickness:

Macroscopic evaluations of tablets from each and every formulation showed a round shape without cracks. Vernier calipers were used to find the thickness of the tablets.

Weight variation:

All the individual formulations passed the weight variation test, the percentage weight variation was within the pharmacopoeia limits of ± 5%. That was found to be from 373.15±1.29 to 377.80±1.82 mg. No formulations have exceeded the limit of ± 5% specified by IP and to comply with the IP standard.

Hardness:

Table .1 containing tablet formulations shows its results for hardness for all tablet formulations. The Hardness was found to be in the range of 5.16±0.12 to 6.75±0.23 kg/cm².

Friability test:

The friability of all the tablets formulations was having been discovered to be in the range of 0.55-0.72%.

Estimation of drug content:

The drug assays values for all the formulations were found to be in the range of 97.62±0.27 to102.47±0.20%.

Mucoadhesive strength:

The mucoadhesion strength of formulations F1, F2, F3, F4, F5, and F6were found to be 16.70±0.25, 17.50±0.40, 18.15±0.35, 19.05±0.25, 20.75±0.20, and 21.40±0.45 N/m2 respectively. The mucoadhesion strength of formulation F7, F8, F9 was found to be 19.10 ±0.30, 22.60±0.16, 23.75±0.30, N/m² respectively. The formulation with higher polymer concentration F9 shows the highest mucoadhesive strength i.e., 23.75±0.30 N/m²; this is due to as the amount of GG increases, the penetration into the mucus layer also increases, and hence mucoadhesion is stronger. All the above results are shown in Table 2.

In-vitro drug release:

The in-vitro drug release characteristic was studied in phosphate buffer pH 6.8 for a period of 8 hrs using USP dissolution apparatus, type-II. The tablet containing Cefixime.T (F1-F9) was prepared. The results of the dissolution studies indicated that the formulations F1, F4, F7 have released 99.55±2.17, 99.39±2.25, 98.91±1.82 percentage of cefixime respectively at the end of 6hrs only. The formulation F1, F4, F7 with a low degree of deacetylation, and low polymer concentration shows a higher cumulative percentage drug release at the end of 6hrs only.

Formulations F2, F3, F5, F6, F8, and F9, released 99.72±1.48, 97.05±1.93, 98.49±1.49, 96.56±1.87, 96.46±1.93, and 91.14±1.63% of cefixime. T at the end of 8 hrs respectively. Formulation F2 choose as the best formulation based on in-vitro drug release studies (figure 2, 3 and 4).

Figure 2: Comparison of dissolution profile of formulation F1-F3

Figure 3: Comparison of dissolution profile of formulation F4-F6

Figure 4: Comparison of dissolution profile of formulation F7-F9

The change in polymer concentration may affect the in-vitro drug release mechanism of the drug from tablets. By increasing polymer concentration, the rate of drug release was decreased, this is due to higher the degree of deacetylation, and therefore the degree of covalent crosslinking increases, higher the degree of crosslinking, increase the compactness of matrices and its hydrophobicity, thus controlling the degree of swelling and diffusivity of the drug entrapped in chitosan matrices. By increasing the polymer concentration, the rate of drug release was decreased due to the unavailability of drug molecules at the surface of tablets.

Model fitting drug release profile of tablet formulation:

Results obtained from in-vitro dissolution studies were evaluated using different mathematical models to describe the kinetics of the drug release from tablets. Release kinetics was evaluated using different kinetic models.

The goodness fit was evaluated using the correlation coefficient values. The in-vitro drug release data of all formulations (F1 to F9) were fitted into zero-order, first order, Higuchi model, and Korsmeyer-Peppas model, and the values of slope (n) and regression coefficient (R) was calculated in each case.

The cefixime. T drug release from the polymeric system is almost by diffusion and it can be best described by non-fickian diffusion. The in-vitro drug release profile of the formulations can be expressed by Higuchi’s kinetics, as it indicates that prepared mucoadhesive tablets drug release was controlled by diffusion (table 3).

Table 3: Zero order, First order, Higuchi and Korsemeyer-peppas model for formulations

Formula	zero-order	First-order	Higuchi	Korsmeyer peppas
F1	0.649	0.268	0.877	0.742
F2	0.777	0.317	0.951	0.693
F3	0.817	0.346	0.968	0.666
F4	0.682	0.286	0.899	0.738
F5	0.722	0.299	0.920	0.690
F6	0.760	0.314	0.941	0.669
F7	0.766	0.344	0.947	0.740
F8	0.840	0.388	0.978	0.701
F9	0.865	0.414	0.987	0.677

DISCUSSION:

The in-vitro studies results indicate that the various polymers and crystallinity of chitosan could responsible for its gel-forming special properties. A special property of chitosan, and its ability to absorb maximum amounts of water on hydration. The findings that the properties could be reflected in the efficacy of gel-forming by chitosan in the tablets formulations. It is a well-known idea that preformed gel formation by a water-soluble polymer was beneficial for the matrix-type and slow-release dosage forms are being well developed. This property was finally related to effects on drug release as a retardant.

The findings were suggested that high drug delivery HPMC combinations with chitosan might be better than the other excipients in the matrix-type and controlled type dosage forms. The rate of release could be controlled by varying the amount of polymers with the combinations of chitosan in tablets. Increasing the amount of polymers decreased the rate of cefixime release from tablets. This finding understood because the increased amount of polymers usually increases the viscosities of gels formed by chitosan. Increasing the percentage of polymers in tablets decreased the rate of drug release.

CONCLUSIONS:

Different polymers with chitosan were usually useful in the preparation of tablets and gels, from which basis, the drug release was controlled by mucoadhesive tablets. The drug release mechanisms of mucoadhesive tablets were diffusion through the matrix and matrix erosion. In all the studied chitosans formulations, the in-vitro mucoadhesive capacities had fairly marked. In-vitro drug release study could be controlled by adding the quantity of chitosan in the formulation. The amount of polymer was important to the tablets, the formulation contains a higher amount of polymer concentration, then slow the rate of drug release, and also the higher the strength of mucus adhesion observed. Chitosan, a promising polymer helpful in the development of mucoadhesive tablets. It depends on the physical properties of chitosan DD and the amount of polymer. In the future, the efficacy of these formulations was going to check after completion of stability studies.

ACKNOWLEDGEMENT:

The authors significantly thank Vaagdevi Pharmacy College Management for providing access to investigate facilities at some stage in the length of the laboratory experiments.

REFERENCES:

1. Sirisolla J, Ramanamurthy KV. Formulation and Evaluation of Cefixime Trihydrate Matrix Tablets Using HPMC, Sodium CMC, Ethyl Cellulose. Indian J Pharm Sci. 2015; 77(3): 321-327.

2. Akelesh T et al. Formulation and Evaluation of Floating Tablets of Cefixime Trihydrate Using Chitosan. Research J. Pharm. and Tech. Nov 2015; 8(11): 1502-1508.

3. Selvakumar S, Ravichandran S, Matsyagiri L. Development and Validation of analytical method for Simultaneous estimation of Ornidazole and Cefixime trihydrate tablet dosage forms by UV spectroscopy. Asian J. Pharm. Ana. 2016; 6(4): 246-252.

4. Dhawan S, Singla AK, Sinha VR. Evaluation of mucoadhesive properties of chitosan microspheres prepared by different methods. AAPS Pharm Sci Tech. Jul 26 2004; 5(4): 67.

5. Vijayanand P, Jagadevappa P, Venkata RM. Formulation, characterization and in vivo evaluation of novel edible dosage form containing nebivolol HCl. 2016; 52, (1); 179-189

6. Rajitha R, Narendar D, Arjun N, Mahipal D and Nagaraj B. Colon delivery of naproxen: preparation, characterization and in vivo evaluation. IJPSN, 2016; 9(3), 1-10.

7. Doodipala R. A review of novel formulation strategies to enhance oral delivery of zaleplon. J Bioequvi avail. 2016; 8(5): 211-213.

8. Arjun N, Narendar D, Sunitha K, Harika K, Madhusudan Rao Y and Nagaraj B. Development, evaluation and influence of formulation and process variables on in vitro performance of oral elementary osmotic device of atenolol. Int J Pharm Invest.2016; 6(4): 1-9.

9. Ettireddy S, Dudhipala N. Influence of β-Cyclodextrin and Hydroxypropyl-β-Cyclodextrin on Enhancement of Solubility and Dissolution of Isradipine. Int J Pharma Sci and Nanotech. 2017;10(3): 3752-7.

10. Palem CR, Reddy ND, Satyanarayana G, Varsha BP. Development and optimization of Atorvastatin calcium-cyclodextrin inclusion complexed oral disintegrating tablets for enhancement of solubility, dissolution, pharmacokinetic and pharmacodynamic activity by central composite design. Int J Pharm Sci Nanotech. 2016; 9(2): 1-11.

11. Butreddy A, Narendar D. Enhancement of solubility and dissolution rate of trandolapril sustained release matrix tablets by liquisolid compact approach. Asian J Pharm. 2015; 9 (4): 290-297.

12. Donthi MR, Dudhipala NR, Komalla DR, Suram D, Banala N. Preparation and Evaluation of Fixed Combination of Ketoprofen Enteric Coated and Famotidine Floating Mini Tablets by Single Unit Encapsulation System. Journal of Bioequivalence and Bioavailability. 2015; 7(6): 279.

13. Reddy N.D, Chinna R.P, Sunil R and Madhusudan Rao Y. Development of floating matrix tablets of Ofloxacin and Ornidazole in combined dosage form: in vitro and in vivo evaluation in healthy human volunteers. Int J Drug Deli.2012; 4, 462-469.

14. Dudipala R, Palem C.R, Reddy S and Madhusudan Rao Y. Pharmaceutical development and clinical pharmacokinetic evaluation of gastroretentive floating matrix tablets of levofloxacin. Int J Pharma Sci and Nanotech.2011; 4(3), 1461-1467.

15. Narendar D, Someshwar K, Arjun N and Madhusudan Rao Y. Quality by design approach for development and optimization of Quetiapine Fumarate effervescent floating matrix tablets for improved oral delivery. J Pharm Investigation.2016; 46(3): 253-263.

16. Vamshi Krishna M, Vijay Kumar B, Narendar D. In-situ Intestinal Absorption and Pharmacokinetic Investigations of Carvedilol Loaded Supersaturated Self-Emulsifying Drug System. Pharm Nanotechnol. 2020; doi: 10.2174/2211738508666200517121637.

17. Dudhipala N, Veerabrahma K. Candesartan cilexetil loaded solid lipid nanoparticles for oral delivery: characterization, pharmacokinetic and pharmacodynamic evaluation. Drug delivery. 2016;23(2): 395-404.

18. Narendar D, and Ahmed Adel AY. Amelioration of ketoconazole in lipid nanoparticles for enhanced antifungal activity and bioavailability through oral administration for management of fungal infections. Chemistry and Physics of Lipids.2020; 232: 104-953.

19. Banala, N, Tirumalesh C, Suram, D. Dudhipala, N. Zotepine loaded lipid nanoparticles for oral delivery: preparation, characterization, and in vivo pharmacokinetic studies. Fut J Pharm Sci.2020; 6(1): 37.

20. Pitta S, Dudhipala N, Narala A and Veerabrahma K. Development and evaluation of Zolmitriptan transfersomes by Box-Behnken design for improved bioavailability by nasal delivery. Drug Dev Ind Pharm.2018; 44(3): 484-492.

21. Narendar D, Riyaz PMD, Ahmed AY, Nagaraj B. Effect of lipid and edge activator concentration on development of Aceclofenac loaded transfersomes gel for transdermal application: in vitro and ex vivo skin permeation. Dru Dev Ind Pharm. 2020. 46(8): 1334-1344.

22. Tirumalesh C, Suram, D, Dudhipala N, Banala N. Enhanced pharmacokinetic activity of Zotepine via nanostructured lipid carrier system in Wistar rats for oral application. Pharm. Nanotechnol. 2020; 8(2): 158-160.

23. Karri V, Butreddy A, Narender R. Fabrication of Efavirenz Freeze Dried Nanocrystals: Formulation, Physicochemical Characterization, In Vitro and Ex Vivo Evaluation. Advanced Science, Engineering and Medicine.2015; 7(5): 385-392.

24. Nagaraj K, Narendar D and Kishan V. Development of Olmesartan medoxomil optimized nanosuspension using the Box–Behnken design to improve oral bioavailability. Drug Dev Ind Pharm, 2017;43(7): 1186-1196.

25. Bindu M B et al. Mucoadhesive drug delivery system: An overview. Journal of Advanced Pharmaceutical Technology and Research. 2011; (1) 4: 381-387.

26. Asha John S et al. Development and evaluation of buccoadhesive drug delivery system for Atorvastatin calcium. Journal of Current Pharmaceutical Research. 2010; 01: 31-38.

27. Yogita R I, Nayana V, Pimpodkar, Puja S G, Anita S G. A Comprehensive Review on Biodegradable Polymers. Asian J. Res. Pharm. Sci. 2016; 6(2): 65-76.

28. Raj Kumar P, Pankaj R, SK Singh, DN Mishra. Bioadhesive Polymers as a Platform for Drug Delivery: Possibilities and Future Trends. Research J. Pharma. Dosage Forms and Tech. 2010; 2(1): 1-6.

29. Narendar D, Arjun N, Karthik Yadav J and Ramesh B. Amoxycillin Trihydrate Floating-Bioadhesive Drug Delivery System for Eradication of Helicobacter pylori: Preparation, In Vitro and Ex Vivo Evaluation. J bioequ avail. 2016; 8(3), 118-124.

30. Babli T, Vinay P, Mahendra Singh A, Pravin Kumar. Natural and Synthetic Polymers for Colon Targeted Drug Delivery. Asian J. Pharm. Tech. 2016; Vol. 6(1): 35-44.

31. Banala N, Peddapalli H, Dudhipala N, Chinnala KM. Transmucosal Delivery of Duloxetine Hydrochloride for Prolonged Release: Preparation, in vitro, ex vivo Characterization and in vitro-ex vivo Correlation. International Journal of Pharmaceutical Sciences and Nanotechnology. 2018 Sep 30; 11(5): 4249-58.

32. Narendar D Ahmed Adel AY, and Nagaraj B. Colloidal lipid nanodispersion enriched hydrogel of antifungal agent for management of fungal infections: comparative in-vitro, ex-vivo and in-vivo evaluation for oral and topical application. Chemistry and Physics of Lipids (2020); 104-981.

33. Krishna Reddy Y, Fathima U. Formulation and Evaluation of Sustained release matrix tablets of Atomoxetine HCl by using Natural and Synthetic Polymers. Asian J. Pharm. Tech. 2020; 10(1): 43-47.

34. Nagaraj B, Anusha K, Narendar D, Sushma P. Formulation and evaluation of microemulsion-based transdermal delivery of duloxetine hydrochloride. International Journal of Pharmaceutical Sciences and Nanotechnology. 2020 Jan 31;13(1): 4773-82.

35. Ahmed AY, Narendar D, Mujumdar S. Ciprofloxacin Loaded Nanostructured Lipid Carriers Incorporated into In-Situ Gels to Improve Management of Bacterial Endophthalmitis. Pharmaceutics. 2020; 12(6): 572.

36. Narendar D, Thirupathi G. Neuroprotective effect of Ropinirole loaded lipid nanoparticles hydrogel for Parkinson’s disease: preparation, in-vitro, ex-vivo, pharmacokinetic and pharmacodynamic evaluation. Pharmaceutics. 2020, 12(5): 448.

37. Somasekhar C et al. Formulation and evaluation of chitosan based effervescent Floating tablets of Verapamil Hydrochloride. IJBPAS. December2012; 1(11): 1711-1720.

38. Manoj Kumar S et al. Chitosan: a novel excipient in pharmaceutical formulation: a review, IJPSR. 2011; 2(9): 2266-2277.

39. Sachin R. K, Zaki Husain J.T, Dr. John I, Souza D. Synthesis and Characterization of Schiff bases of Chitosan for their Improved Mucoadhesion. Asian J. Research Chem. 5(9): September, 2012; Page 1099-1103.

40. Younes I, Rinaudo M. Chitin and chitosan preparation from marine sources. Structure, properties and applications. Mar Drugs. 2015; 13(3): 1133-1174.

41. Durgesh Kumari G, Goswami R, Deepak K, Anjana G, ChandySteffy M. A Review on Chitosan Nanoparticle as a Drug delivery system. Asian J. Pharm. Res. 2020; 10(4): 299-306.

42. The United States Pharmacopeia. The National Formulary 1990, USP XXII. P. 887-889, 1578.

43. Indian Pharmacopoeia. 1996; 2:S-62: 486-487.

44. Lachman L, Lieberman HA. The Theory and Practice of Industrial Pharmacy. Special Indian edition. 2009.

45. Chinna Reddy P, Ramesh G, Narender D, Vamshi Vishnu Y, and Madhusudan Rao Y. Transmucosal Delivery of Domperidone from Bilayered Buccal Patches: In-Vitro, Ex- Vivo and In-Vivo Characterization. Arch Pharm Res.2011; 34(10): 1701-1710.

46. Salunke P A, Umarkar A R, Bagad Y M, Bawaskar S R, and Sonawane R O. Simultaneous Estimation of CefiximeTrihydrate and Ofloxacin by UV Spectrophotometer Using Multicomponent Method. Asian J. Research Chem. May 2011; 4(5): Page 708-710.

47. Chinna Reddy P, Narendar D, Sunil Kumar B, Michael AR and Madhusudan Rao Y. Development, Optimization and in-vivo Characterization of Domperidone Controlled Release Hot Melt Extruded Films for Buccal Delivery. Drug Dev Ind Pharm, 2016; 42(3), 473-484.

48. Chinna Reddy P, Narendar D, Sunil Kumar B, Satyanarayana G, and Madhusudan Rao Y. Combined dosage form of Pioglitazone and Felodipine as mucoadhesive pellets via hot melt extrusion for improved buccal delivery with application of quality by design approach. J Drug Del Sci Tech. 2015; 30: 209-219.

49. Park H, Robinson JR. Mechanisms of mucoadhesion of poly (acrylic acid) hydrogels. Pharm Res. 1987; 4: 457-464.

50. Donthi MR, Dudipala N, Komalla DR, Suram D, Banala N. Design and Evaluation of Floating Multi Unit Mini Tablets (MUMTS) Muco Adhesive Drug Delivery System of Famotidine to Treat Upper Gastro Intestinal Ulcers. Journal of Pharmacovigilance. 2015 Oct 12.

51. Manish P, Patel MM, Patel KN, Patel DR, Patel UL. Designing and Evaluation of Floating Microspheres of Verapamil Hydrochloride: Effect of Methocel. Research J. Pharma. Dosage Forms and Tech. 2009; 1(1): 22-28.

52. Dinesh D, Amit A R, Maria S, Swaroop R L and Mohd. Hassan G D. Development and In Vitro Evaluation of Oral Floating Matrix Tablet Formulation of Ranitidine Hydrochloride. Research J. Pharma. Dosage Forms and Tech. 2009; 1(1): 41-44.

53. Raj kumar P, Pankaj R, Singh SK, Mishra DN. Bioadhesive polymers as a platform for drug delivery: possibilities and future trends. Research Journal of Pharmaceutical Dosage Forms and Technology. 2009; 1(3): 280-284

54. Navneet N, Manisha A, Sandeep R, Swami G, Sharma D and Kapoor R. Mucoadhesion Based Solid Dosage Form: The Next Generation. Research J. Pharma. Dosage Forms and Tech. 2010; 2(5): 323-328.

55. Ranabir Ch, Mahapatro S.K, Tutun, Amit R and Sanjib B. Development of Oral Mucoadhesive Tablets of Terbutaline Sulphate Using Some Natural Materials Extracted from Albelmoschus esculeatus and Tamarindus indica. Research J. Pharm. and Tech.2008; 1(1): 46-51.

56. Venkatalakshmi R, Tan SH, Prasanthi S. Formulation and Evaluation of Buccal Tablets of Diclofenac Sodium using Semi-Synthetic Polymers. Research J. Pharm. and Tech. 2018; 11(1): 01-08

57. Annapurna U, Naga Swapna V, Neelima Devi R, Glory Sheren G, Kishore Kumar B. Formulation and Evaluation of Mucoadhesive Buccal Films of Diclofenac Potassium. Research J. Pharm. and Tech. 8(9): Sept, 2015; Page 1269-1275.

58. Sheetal D and Varsha P. Formulation Development of Mucoadhesive Matrix Tablet for Metformin Hydrochloride: In-Vitro and In-Vivo Evaluation. Research J. Pharm. and Tech. 2010; 3(2): 443-450.

59. Patil CC, Pawar VV, Karajgi SR, Kalyane NV. Formulation and Evaluation of Mucoadhesive Buccal Tablets of Ondansetron Hydrochloride. Research J. Pharm. and Tech 2018; 11(2): 581-586.

Received on 06.01.2021 Modified on 20.02.2021

Res. J. Pharma. Dosage Forms and Tech.2021; 13(3):167-173.

DOI: 10.52711/0975-4377.2021.00030

Formula	Hardness (Kg/cm²)	Friabilty (%)	Weight Variation (mg)	Thickness (mm)	Assay (%)	Mucoadhesive Strength (gm)
F1	6.33±0.12	0.62	375.15	4.29±0.35	98.36±0.23	16.70±0.25
F2	6.51±0.19	0.68	376.33	4.54±0.15	97.62±0.27	17.50±0.40
F3	6.25±0.15	0.58	377.25	4.25±0.22	101.25±0.18	18.15±0.35
F4	6.75±0.23	0.72	373.15	4.62±0.18	99.21±0.27	19.05±0.25
F5	5.16±0.15	0.55	374.31	4.22±0.25	98.11±0.13	20.75±0.20
F6	6.25±0.10	0.66	377.80	4.78±0.16	102.47±0.20	21.40±0.45
F7	5.60±0.25	0.55	374.63	4.89±0.33	98.68± 0.16	19.10 ±0.30
F8	6.75±0.15	0.64	375.96	4.16±0.12	101.36±0.21	22.60±0.16
F9	6.55±0.10	0.59	374.48	4.29±0.11	99.48±0.18	23.75±0.30

n is the diffusion exponent for the release and it depends on that shape of the matrix dosage form. If n < 0.45, Fickian diffusion mediated drug release occurs58. Non- Fickian release occurs if 0.45< n<0.89 and erosion59 (i.e. complete matrix relaxation) mediated release occurs in n=0.89.

RESULTS AND DISCUSSIONS:

n is the diffusion exponent for the release and it depends on that shape of the matrix dosage form. If n < 0.45, Fickian diffusion mediated drug release occurs⁵⁸. Non- Fickian release occurs if 0.45< n<0.89 and erosion⁵⁹ (i.e. complete matrix relaxation) mediated release occurs in n=0.89.