INTRODUCTION:

Azithromycin is an eminent macrolide antibiotic of adequate potency and is widely used for the treatment of upper and lower respiratory tract infections. Pulmonary and Nasal routes have major drawbacks like dose variation, lack of patient compliance, etc.¹ In vivid types of oral dosage forms, Azithromycin has an absolute oral bioavailability of about 34-52% when given in single doses ranging from 500 mg to 1.2 g. Research evidence suggests that owing to acid degradation of API or hepatic first pass metabolism limits the GI absorption and is the root cause of its poor bioavailability.^2,3

Drug delivery via the buccal route can be a promising approach to treat upper respiratory tract infections as it increases the bioavailability of the drug. The mucoadhesive buccal tablet offers extensive surface area in the buccal region thus prolonging release characteristics with a targeted approach.

Mucoadhesive dosage forms are popular because they can enhance localisation of the dosage form at the target site.^4,5,6 Mucoadhesives are natural or synthetic polymers that are also suitable for delivery of complex drugs, which establish interactions and create linkages with the mucus layer that coats the surface of the mucosal epithelial cells.^7,8 After placing the mucoadhesive buccal tablets in buccal socket, interaction with the buccal mucosa takes place, where they are to be moistened.^9,10 The objective of this experimental study was to develop buccal tablet formulations of Azithromycin dihydrate, in order to treat upper respiratory tract infections.

MATERIAL AND METHOD:

Material:

Drugs and Chemicals:

The ingredients used in the formulation and development were Azithromycin Dihydrate USP obtained as a gift sample from Ajanta Pharmaceuticals (Mumbai, India), aspartame and magnesium stearate were received from Chemco (India), Carbopol 971P NF (Lubrizol India), Pectin GENU Slow Set 121GENU Slow Set 121 (CP Kleco), and Colloidal Silicon Dioxide (Evonik Industries). The chemicals were compliant with IP/BP/USP or in-house specifications.

Method of mucoadhesive tablet development:

Formulation and development of mucoadhesive buccal tablet:

Mucoadhesive buccal tablets were prepared using the direct compression method in Multi Punch Tablet Compression Machine (Rimek).¹¹ Different ratios of natural and synthetic mucoadhesive polymers and glidant were selected and a fixed amount of drug, sweetener, anti-adherent and lubricant were added as given in Table No. 1 and mixed well. The blend was compressed directly using the appropriate die cavity and punch based on the individual tablet weight. The prepared batches were evaluated for mucoadhesive strength, swelling studies, surface pH properties, and other post-compression properties.

Optimization of the mucoadhesive buccal tablets was done by three factorial designs using design expert software version 12. The different batches, each having different ratios of pectin, carbopol, and silicon dioxide, were studied to understand the required higher and lower levels to be used for the optimization process.

Characterization of pre optimized batch and optimized batch:

Pre-compression properties¹:

a) Bulk density:

Approximately 10grams of the quantified powder blend was meticulously transferred into a graduated cylinder. The blend was then leveled and the volumetric displacement of the powder, denoted in milliliters, was documented according to the demarcations present on the cylinder. The density of the blend was then determined, expressed in grams per milliliter (gm/ml), using the mathematicalexpression,

Bulk density = Mass/ Bulk volume

b) Tap density:

Tapped density is the quotient derived from the weight of the powder and its corresponding volume after tapping. A graduated cylinder, filled with a precisely measured quantity of powder, was utilized with the tap density apparatus. The volumetric displacement caused by the powder was duly noted. This value is articulated in gm/ml, and the following equation was utilized for the computation of tapped density,

Tapped density = Mass/ Tapped volume

c) Carr’s index and Hausner ratio¹²:

Carr's Index or Compressibility Index and Hausner ratio measures the powders property to be compressed and its flowability. These values were determined employing the subsequent formula: -

Compressibility Index (I) = Dt – Db/ Dt × 100

Hausner ratio = Dt / Db

Where, Dt = Tapped density of the powder

Db = Bulk density of the powder

d) Angle of repose:

The highest angle that can be made between a pile of powder's surface and the horizontal plane allows for the measurement of frictional forces in loose powder is the angle of repose. An ample volume of powder integrated with excipients was carefully dispensed from a funnel stationed at a fixed elevation (2 cm) onto a horizontal plane. This process was continued until a heap of powder was constituted, extending to the level of the funnel's tip. Subsequent measurements were taken for both the height and radius of the resultant powder heap. The derived values were then computed using the following mathematical equation -

Angle of repose (θ) = tan^-1 (h/r)

Where, h = Height of pile in cm

r = Radius of the pile

Azithromycin mucoadhesive buccal tablet compression properties:

· Weight Variation

A randomized selection of 20 tablets from the optimized batch, conforming to the IP standards, were individually weighed. The mean weight of these tablets was then calculated utilizing a high-precision digital balance.¹³

· Thickness:

The thickness of the randomly selected buccal tablets were measured using Vernier calliper. ¹⁴

· Friability:

Tablets with initial weight of 6.5 gm were chosen from each prepared batch and weighed individually (W initial) before being placed in the friability device, which was subsequently turned 100 times at a speed of 25 rpm. The tablets were weighed again after the process (W final), and the following formula was used to determine each batch's percentage of friability (F).¹⁵

Friability = {[W initial] – [W final] / [W initial]} × 100

· Hardness:

Hardness was evaluated using Monsanto hardness tester.¹⁶ The tablet was placed between the fixed jaw and moving jaw desired amount force applied using screw knob the force at which tablet breaks was recorded as hardness of the tablet. ¹⁷

· Drug Content:

The tablets were triturated using mortar and pestle mass equivalent to 200 mg of Azithromycin was weighed. This powder was dissolved in 0.1 M HCl solution was filtered, and the content was evaluated for UV analysis.

· Mucoadhesive Strength:

Ex vivo mucoadhesive strength was determined by using the modified mucoadhesive apparatus described by Agarwal andMishra et al ¹⁸ for measuring the mucoadhesive strength of the formulation. Fresh cut sheep buccal mucosa obtained within 2 hours from a slaughter-house. Followed with the detachment of the mucosal membrane from the associated adipose and loose tissue, the membranes were rinsed and cleaned with distilled water, and subsequently, with a phosphate buffer of pH 6.0.

Tissue holder required its surface was made up of plexiglass, a rectangular piece of buccal mucosa was cut and adhered using cyanoacrylate adhesive. This buccal mucosa was pasted to the other side of a tissue holder that was the same size. Following this, a pH 6.0 buffer media was applied to the buccal tablet in a petri dish for 10 seconds. The tissue holders holding the buccal mucosa and formulation were then placed in contact with one another under a uniform and constant amount of pressure for 30 seconds (preload time) to aid in system adhesion. The buccal mucosa and tissue holder were allowed to suspend from an iron stand using an aluminium wire fastened to the hook on the rear side of the holder. Aluminium wire was used to secure a preweighed lightweight polypropylene bottle to the hook on the back of the formulation holder. Water was infused into the polypropylene bottle using an intravenous infusion set at a rate of one drop per second after a preload period of 30 seconds, until the mucoadhesive system separated from the buccal mucosa membrane. The accumulated water in the bottle was carefully examined, measured, and reported as weight (g) required for the detachment, thus indicating the mucoadhesive strength.

· Surface pH

The possibility of side effects in vivo can be investigated by determining the surface pH.¹⁹ The surface pH of the buccal tablets was determined using the surface pH method.²⁰ For 10 minutes at room temperature, the tablet was immersed in 1 mL of phosphate buffer, pH 6.0, and allowed to swell. The determination of pH was conducted by positioning the pH electrode near the surface of the tablet and permitting it to remain for a duration of one minute, following this procedure the readings were documented.

· Swelling index

The tablet was placed in 5ml of the pH 6.0 phosphate buffer media in a small glass beaker after 1 hour it was taken out and re-weighed.^21,22

Swelling Index = (Wt-Wo)/W_O

Where Wt = Tablet weight at time (t)

Wo = Initial weight of the tablet

· Ex vivo residence time:

Freshly cut sheep's buccal mucosa was sized and glued with cyanoacrylate adhesive to the glass surface made of plexiglass. The mucoadhesive system was wetted with some buffer (pH 6.0) and brought into contact with the buccal mucosa. This slide was slowly vertically immersed from the sides into a beaker containing 250 ml of buffer media, placed on a magnetic stirrer and the needle rotating at the speed of 150 rpm at room temperature. The total time needed for the tablet to completely erode or disengage from the mucosal surface was measured and regarded as the ex vivo residence time of the mucoadhesive system.¹⁷

· In vitro dissolution studies:

For in vitro dissolution studies, a modified USP type 2 paddle apparatus (Electro Lab) was used, and mucoadhesive buccal tablets and commercial tablets were dissolved in 250 ml of phosphate buffer pH 6.0, spinning at 50 rpm at 37°C±1℃.²³At specific time points (1, 2, 4, 6, 8 hours), 10 ml samples were withdrawn using a syringe and immediately replaced with fresh phosphate buffer media to maintain sink conditions. These withdrawn samples were subsequently filtered through a PVDF HPLC syringe filter with a pore size of 0.2 µm and then transferred into type 1 glass vials. From the filtered samples, 0.5 ml was extracted using a 1 ml syringe and transferred to a clean, dry 5 ml volumetric flask. To this sample, 2.5 ml of concentrated H2SO4 (18M) was added, and the volume was adjusted using distilled water. After preparing the dilutions, they were kept stable at 25ºC for 1 hour. A yellow solution was obtained, and absorbance was measured at a constant wavelength of 480 nm with a UV-Visible spectrophotometer (UV-550 Thermo evolution scientific).²⁴

· Stability Studies:

The mucoadhesive buccal tablets were packaged in firmly closed aluminium foils to prevent moisture from penetration into the package. These tablets underwent stability testing at ambient temperature and at an accelerated temperature of 40°C for 1, 2, and 3 months. The following characteristics were assessed: hardness, friability, surface pH, drug content, cumulative drug release, and mucoadhesive strength.

Table no 1: Formulation table for pre optimized batch (prepared batches)

Sr. No.	Ingredients	F1	F2	F3	F4	F5	F6	F7	F8
1	Azithromycin dihydrate	Azithromycin dihydrate USP equivalent to 100mg of Azithromycin
2	Aspartame	20	20	20	20	20	20	20	20
3	Pectin GENU Slow Set 121	25	75	75	25	75	25	75	25
4	Carbopol	10	10	30	30	10	10	30	30
5	Silicon dioxide	2.5%	2.5%	1.5%	1.5%	1.5%	1.5%	2.5%	2.5%
6	Magnesium Stearate	1%	1%	1%	1%	1%	1%	1%	1%

Table no 2: Formulation of optimized batch

Sr. No.	Ingredients	Formula for 1 tablet (mg)	Uses
1	Azithromycin Dihydrate	Azithromycin Dihydrate (USP equivalent to 100mg of Azithromycin)	Drug
2	Aspartame	20	Sweetener
3	Pectin GENU Slow Set 121	73.41	Hydrophilic Polymer
4	Carbopol 971 P NF	18.08	Mucoadhesive Polymer
5	Silicon dioxide	2.48%	Glidant
6	Magnesium stearate	1%	Lubricant

Characterization of pre optimized batch and optimized batch

Table no 3: Characterization of pre optimized batch and optimized batch

Sr. No.	Characterization	Formulation Code
Sr. No.	Characterization	F1	F2	F3	F4	F5	F6	F7	F8	Optimized batch
1.	% Drug content	101.25	99.23	92.51	99.37	98.99	101.47	100.25	100.56	99.1
2.	Friability %	0.66	0.53	0.84	0.55	0.29	0.96	0.76	0.96	0.592
3.	Swelling index %	57.97	44.39	81.22	119.48	55.85	82.26	102	55.08	70.33
4.	Surface pH	6.03	6.05	6.04	6.03	6	6.05	6.02	6	6.03
5.	% Cumulative percent release at 8 hours	88.89	88.06	61.56	56.4	95.84	90.91	66.21	55.55	79.63
6.	Mucoadhesion gm	2.38	3.59	4.37	4.9	2.58	2.26	7.7	4.94	4.82
7.	In vitro residence time hours	14	18	36	48	12	14	40	48	48

DISCUSSION:

An effective mucoadhesive tablet should exhibit an instantaneous as well an extended pharmacological response to promote sustained drug release and provide sufficient time to occupy the buccal cavity before being consumed.²⁵

Drug- excipient studies were performed out with the use of FT-IR-Fourier Transform Infrared Spectrophotometer (Bruker) and all the IR peak characteristicsof the drug and excipient were observed after mixing andno interaction were observed.

Formulation of pre-optimized batches were prepared according to Table No. 1 and 21 suggestions were generated in the Design of Expert software version 12. Amongst those suggestions, the batch having desirability equal to 1 was selected as the optimized batch. The optimised batch was formulated using the values mentioned in Table No. 2. The ANOVA was performed and it was found to be significant. A 3D model of dissolution and mucoadhesion were observed as seen in Figures No. 1 and 2. Analysis was done on the relative dissolution of pre-optimized batch and optimised batch (Figures 3 and 4).

The pre-optimized batch with formulation code F4 with maximum bulk density of 0.44gm/cc and formulation code with F2 showed lowest bulk density of 0.28gm/cc. It was reported that silicon dioxide plays a key role which affects the bulk density when there was high amount of silicon dioxide in F4 and low in F2. The bulk density for optimized batch was found to be 0.28 gm/cc as seen in Table no. 3. In pre-optimized batch the highest tap density was 0.52gm/cc for F4 and the lowest was 0.36gm/cc for F2. It was understood that polymers and glidant influenced the tap density parameters. For an optimized batch, it was found to be 0.42gm/cc. In the pre-optimized batch with a high concentration of Pectin GENU Slow Set 121and Carbopol 971P, viz., F7 and F3, showed higher percent compressibility. Pectin GENU Slow Set 121had the highest impact on flow properties. The higher the quantity of pectin, the poorer the flow. All tablets had an optimum organoleptic property. Tablets were free of roughness, flat-faced, plane, very light brown, and round with no apparent tablet defects. Trial batches, pre-optimized batches and optimized batches passed the drug content assay as per IP. The hardness of the tablet was kept constant through the study, which was 5kg/cm² and the fixed diameter was 10mm for pre-optimized batch and optimized batch. As the amount of formulation per tablet varied, the thickness also varied. The friability records of pre-optimized and optimized batches were below 1%. The pre-optimized batch with formulation code F8 and F6 showed maximum friability of 0.96%, which was due to a lower amount of pectin. A higher amount of Pectin GENU Slow Set 121was responsible for keeping the tablet structure intact. The optimized batch showed a friability value of 0.59%. The pre-optimized and optimized batches passed the weight variation test, and they were within the IP limits.

Swelling index of F7 batch was 102 % with relatively higher amount of carbopol, Pectin GENU Slow Set 121 and silicon dioxide. Silicon dioxide allowed the formation of pores leading to swelling of the polymer (Carbopol 971 P NF) and the Pectin GENU Slow Set 121was able to hold the tablet structure intact as well as the hydrophobic nature of silicon dioxide caused holes when they were kept in contact with buffer medium. But in case of formulation F4 as reported containing low concentration of Pectin GENU Slow Set 121and silicon dioxide, the swelling index was high with 119.48% due to more surface area available and also there was detoriation in the tablet structure.

The measured pH of the surface ofmucoadhesive buccal tablet was found to be closer to the physiological pH 5.5 to 7.0 of the buccal mucosa and the formulation variables had little effect on the tablet's surface pH for pre-optimized and optimised batches.

The in vitro residence time limit for the mucoadhesive buccal tablets was 8 hours. Pre-optimized and optimized batches were within the limit. Pre-optimized batch F8 had highest residence time of 48hours. The primary reason was the high amount of Carbopol 971 P NF interacting with the buccal mucosa. The mucoadhesive strength was influenced by amount of polymer present. The batch with highest quantity of polymers F7 showed highest mucoadhesion of 7.7gm and batch with lowest quantity of polymers showed lowest mucoadhesion of 2.38gm. Among the polymers, Carbopol 971 P NF had maximum influence on mucoadhesion. Carbopol 971 P NF was effective even in low quantity.²⁶ This may be due to the strong hydrogen bonding of Carbopol 971 P NF with mucin. Also, polymeric chains present in it are responsible for increased entanglement and interpenetration at the interfacial region of mucosa.²⁷

The Mucoadhesive buccal tablets were prepared using direct compression method showed the zero-order kinetic release based upon the matrix-based erosion. The minimal drug release was 55.55% for F8 batch which had high amount of Carbopol 971 P NF and relatively less amount of Pectin GENU Slow Set 121and high amount of silicon dioxide which clearly indicated the slow swelling and prolong release nature of the drug from this system. Maximum release of 95.84% for F5 batch at 8hours which had high amount of Pectin GENU Slow Set 121and low amount of Carbopol 971 P NF and silicon dioxide. The drug release from the optimized batch was observed to be 79.63%. which mostly followed the swelling-based release mechanism. When all these excipients were used at the greater strength, the tablets showed a good swelling index but poor release characteristics.

Lowering the Carbopol 971 P NF amount was able to give optimum prolonged release characteristics. A higher concentration of Pectin GENU Slow Set 121helped to improve the flow property and hardness of the tablet. It was reported that an increase in the amount of silicon dioxide leads to the formation of pores resulting in rapid swelling. The optimized tablet prepared by numerical method passed the specification and showed release of 80% at 8hours (R² zero-order 0.998 first order-0.957 Higuchi 0.9806 Hixon crowell-0.9801 and Korsmeyer peppas 0.8026) (Figure No. 5) and stability studies for the optimized batch were carried out at room temperature and accelerated temperature, no significant changes were recognized, and the formulation was found to be stable (Table No. 4).

CONCLUSION:

Mucoadhesive buccal tablet containing Azithromycin dihydrate for upper respiratory tract infection was successfully formulated. Mucoadhesive buccal tablet system was developed using a combination of natural and synthetic polymer as well with glidant to provide desired quality tablets in terms of adhesion and drug release.They were also evaluated for weight variation, thickness, friability, hardness, drug content, mucoadhesive strength, surface pH, swelling index, ex vivo residence time as well as in vitro dissolution studies were performed on formulated batches. Stability studies were also performed and the mucoadhesive buccal tablets were found to be stable.

CONFLICTS OF INTEREST:

The authors have no conflict of interest regarding this investigation.

ACKNOWLEDGEMENTS:

We would like to acknowledge Principal K.M. Kundnani College of Pharmacy for providing instrument facility under DST-FIST Funding (Letter SR/FST/College-264 dated 18th November 2015).

REFERENCES:

1. Touitou E, Illum L. Nasal drug delivery. Drug Delivery and Translational Research. 2013; 3(1): 1-3. https://doi.org/10.1007/s13346-012-0111-1.

2. American Society of Health 4 System Pharmacists 2012; Drug Information. 2012. Bethesda, MD. 2012, p. 240

3. Nagaveni P, Sirisha S, Rao CA. Formulation and evaluation of mucoadhesive buccal tablets of anti-diabetic drug using 23 factorial design. Asian Journal of Pharmacy and Technology. 2021;11(4):261-6.

4. Li KL, Castillo AL. Formulation and evaluation of a mucoadhesive buccal tablet of mefenamic acid. Brazilian Journal of Pharmaceutical Sciences. 2020; 56. https://doi.org/10.1590/s2175-97902019000418575.

5. Semalty M, Semalty A, Kumar G. Formulation and characterization of mucoadhesive buccal films of glipizide. Indian Journal of Pharmaceutical Sciences. 2008; 70(1): 43. https://doi: 10.4103/0250-474X.40330

6. Begum SK, Sura RS, Phanindra B, Kumar PP. Formulation and Evaluation of Mucoadhesive Buccal Tablets of Captopril. Research Journal of Pharmaceutical Dosage Forms and Technology. 2019; 11(3): 164-8.

7. Singh SK, Bothara SB, Singh S, Patel R, Dodia R. Formulation and Evaluation of Mucoadhesive Tablet: Influence of Some Hydrophilic Polymers on the Release Rate and In Vitro Evaluation. International Journal of Pharmaceutical Sciences and Nanotechnology. 2010; 3(3): 1111-21. https://doi.org/10.37285/ijpsn.2010.3.3.9

8. Khazaal AA, Samein LH, Shehab MA. Preparation and in-vitro evaluation of zolmitriptan mucoadhesive buccal tablets. Research Journal of Pharmacy and Technology. 2012; 5(10): 9.

9. Singh J, Deep P. A review article on mucoadhesive buccal drug delivery system. International Journal of Pharmaceutical Sciences and Research. 2013; 4(3): 916.

10. Nagaveni P, Sirisha S, Rao CA. A Complete Review on Mucoadhesive Buccal Tablets. Research Journal of Pharmaceutical Dosage Forms and Technology. 2021; 13(2): 121-6.

11. Balamurugan M, Saravanan VS, Ganesh P, Senthil SP, Hemalatha PV, Pandya S. Development and in-vitro evaluation of mucoadhesive buccal tablets of domperidone. Research Journal of Pharmacy and Technology. 2008; 1(4): 377-80.

12. Amballa H, Kaluva N, Beri SG, Chinnala KM, Konda M. Formulation and characterization of eplerenone mucoadhesive buccal tablets. Research Journal of Pharmacy and Technology. 2021; 14(6):3097-103.

13. Razzaq S, Hanif S, Syed MA, Iqbal J, Raza SA, Riaz H, Abid F. Development and evaluation of mucoadhesive buccal tablet containing metronidazole for the treatment of periodontitis and gingivitis. Pakistan Journal of Pharmaceutical Sciences. 2018; 31(5).

14. Ramana MV, Nagda C, Himaja M. Design and evaluation of mucoadhesive buccal drug delivery systems containing metoprolol tartrate. Indian Journal of Pharmaceutical Sciences. 2007;69(4):515.

15. Koirala S, Nepal P, Ghimire G, Basnet R, Rawat I, Dahal A, Pandey J, Parajuli-Baral K. Formulation and evaluation of mucoadhesive buccal tablets of aceclofenac. Heliyon. 2021; 7(3): e06439. https://doi.org/10.1016/j.heliyon.2021.e06439.

16. Shanker G, Kumar CK, Gonugunta CS, Kumar BV, Veerareddy PR. Formulation and evaluation of bioadhesive buccal drug delivery of tizanidine hydrochloride tablets. AAPS Pharmscitech. 2009; 10(2): 530-9.

17. Dasari N, Vaddi H, Muvvala S. Formulation and evaluation of mucoadhesive buccal tablets of resperidone. Asian Journal of Pharmacy and Technology. 2022;12(1):13-9.

18. Agarwal V, Mishra B. Design, development, and biopharmaceutical properties of buccoadhesive compacts of pentazocine. Drug Development and Industrial Pharmacy. 1999; 25(6): 701-9. https://doi.org/10.1081/DDC-100102229.

19. Umarji B, Patil R, Birajdar R, Mysore S, Bilagi S, Audurti D. Formulation and in vitro evaluation of mucoadhesive buccal tablets of furosemide. World J. Pharm. Pharm. Sci. 2012; 1(3): 1041-63.

20. Patil CC, Pawar VV, Karajgi SR, Kalyane NV. Formulation and Evaluation of Mucoadhesive Buccal Tablets of Ondansetron Hydrochloride. Res J. Pharm. Tech. 2018 ; 11(2): 581-6.

21. Saleem MA, Pange SS, Umair SA, Singh VK. Development and Evaluation of Mucoadhesive Buccal Tablets of Sumatriptan Succinate using Natural Gums. Research Journal of Pharmacy and Technology. 2011; 4(7): 1140-6.

22. Manivannan R, Balasubramaniam A, Anand DC, Sandeep G, Rajkumar N. Formulation and in vitro evaluation of mucoadhesive buccal tablets of diltiazem hydrochloride. Res J Pharm Tech. 2008; 1(4): 478-80.

23. Karki D, Kulkarni GS, Swamy S, Sheeba FR. Formulation and evaluation of mucoadhesive buccal tablets of curcumin and its bioavailability study. Research Journal of Pharmacy and Technology. 2017; 10(12): 4121-8.

24. Shanker G, Kumar CK, Gonugunta CS, Kumar BV, Veerareddy PR. Formulation and evaluation of bioadhesive buccal drug delivery of tizanidine hydrochloride tablets. AAPS Pharmscitech. 2009; 10(2): 530-9. https://doi.org/10.1208/s12249-009-9241-2.

25. Vaidya VM, Manwar JV, Mahajan NM, Sakarkar DM. Design and in vitro evaluation of mucoadhesive buccal tablets of terbutaline sulphate. Int J PharmTech Res. 2009; 1(3): 588-97.

26. Bahri-Najafi R, Rezaei Z, Peykanpour M, Shabab L, Solooki R, Akbari P. Formulation of nicotine mucoadhesive tablet for smoking cessation and evaluation of its pharmaceutical’s properties. Advanced Biomedical Research. 2013; 2.

27. Patel H, Srinatha A, Sridhar BK. External cross-linked mucoadhesive microbeads for prolonged drug release: development and in vitro characterization. Indian Journal of Pharmaceutical Sciences. 2014; 76(5): 437.

Received on 03.10.2022 Modified on 11.04.2023

Research J. Pharm. and Tech 2024; 17(3):1033-1039.

DOI: 10.52711/0974-360X.2024.00160

Parameters	30 Days		60 days		90 days
Parameters	RT	40ºC	RT	40ºC	RT	40ºC
Hardness	5	5	5	5	5	5
Friability	0.55	0.46	0.49	0.50	0.44	0.51
%Drug content	98.66	99.78	101.23	100.32	99.12	99.54
Surface pH	6.01	6.0	6.0	6.0	6.02	6.0
%Drug Release	79.88	80.01	80	80	80.03	80
Mucoadhesive Strength	4.88	4.78	4.9	4.85	4.82	4.85

MATERIAL AND METHOD:

Material:

Drugs and Chemicals:

Characterization of pre optimized batch and optimized batch:

Pre-compression properties¹:

a) Bulk density:

b) Tap density:

c) Carr’s index and Hausner ratio¹²:

d) Angle of repose:

Azithromycin mucoadhesive buccal tablet compression properties:

· Weight Variation

· Thickness:

· Friability:

· Hardness:

· Drug Content:

· Mucoadhesive Strength:

· Ex vivo residence time:

· In vitro dissolution studies:

· Stability Studies:

Characterization of pre optimized batch and optimized batch

Table no 3: Characterization of pre optimized batch and optimized batch

Analysis of response variables:

Comparative dissolution of pre optimized batch

Optimized batch dissolution:

Figure No. 4: Optimized batch in vitro dissolution

Zero order kinetic release for optimized batch

Stability Studies:

DISCUSSION:

CONCLUSION:

ACKNOWLEDGEMENTS:

REFERENCES:

MATERIAL AND METHOD:

Material:

Drugs and Chemicals:

Characterization of pre optimized batch and optimized batch:

Pre-compression properties1:

a) Bulk density:

b) Tap density:

c) Carr’s index and Hausner ratio12:

d) Angle of repose:

Azithromycin mucoadhesive buccal tablet compression properties:

· Weight Variation

· Thickness:

· Friability:

· Hardness:

· Drug Content:

· Mucoadhesive Strength:

· Ex vivo residence time:

· In vitro dissolution studies:

· Stability Studies:

Characterization of pre optimized batch and optimized batch

Table no 3: Characterization of pre optimized batch and optimized batch

Analysis of response variables:

Comparative dissolution of pre optimized batch

Optimized batch dissolution:

Figure No. 4: Optimized batch in vitro dissolution

Zero order kinetic release for optimized batch

Stability Studies:

DISCUSSION:

CONCLUSION:

ACKNOWLEDGEMENTS:

REFERENCES:

Pre-compression properties¹:

c) Carr’s index and Hausner ratio¹²: