INTRODUCTION:

In the last decade considerable interest has been focused on buccal drug delivery systems using the oral mucosal cavity as an attractive administration route. Several advantages such as relative permeability, robustness and short recovery after stress or damage are related to mucous membrane. However, oral mucosa has been considered advantageous to the oral route because they bypass the hepatic first-pass effect and pre-systemic metabolism into the gastrointestinal track. Furthermore, drug absorption can be discontinued in the case of toxic effects by discharging the formulation from the buccal cavity. Bioadhesive formulations have been developed to enhance the bioavailability of drugs that undergo substantial first-pass hepatic effect and to control the drug release to a constant rate^1.

Buccal administration of drugs which exhibit a low oral bioavailability is a useful method to achieve higher bioavailability. Sublingual tablet and chewing gum are widely used systems but upon their administration a large proportion of the administered dose can be swallowed before being absorbed. It is proposed that a sustained release bioadhesive tablet can help to avoid this undesirable effect and also exhibit a longer duration of action without any harmful reaction with large contact area of oral mucosa².

In addition the drug is protected from degradation due to pH and digestive enzymes of the middle gastrointestinal tract and also hepatic first pass metabolism, improved patient compliance due to the elimination of associated pain with injections, administration of drugs in unconscious or less co-operative patent convenience of administration as compared to injections or other oral medications and a relatively fast onset of action can be achieved relatively to the oral route and the formulation can be removed if therapy is required to be discontinued. The broad contact surface area of the oral cavity helped to fast and extensive drug absorption^{3, 4}. Prunus amygdalus gum is a novel polysaccharide; physico-chemical characterization was performed earlier by Srikanth et al in order to establish its suitability as pharmaceutical excipient. Srikanth et al. developed gastric floating matrix tablets of propranolol hydrochloride and concluded that the gum has good swelling nature with drug release retarding property and can be used as a controlled release polymer5, 6. Propranolol hydrochloride (PPPNL HCl) act as a beta non selective adrenergic blocking agent specifically competes with beta-adrenergic receptor agonist agents for available receptor sites. It works by reducing the amount of work the heart has to do (reduces chest pain) and the amount of blood the heart pumps out (lowers high blood pressure). PPPNL HCl has low oral bioavailability and short half life and extensive hepatic first pass metabolism those are affected the performance of the drug. Propranolol is highly lipophilic and almost completely absorbed after oral administration. However, it undergoes high first-pass metabolism by the liver and on average, only about 25% of propranolol reaches the systemic circulation. Peak plasma concentrations occur about 1 to 4 hours after an oral dose. Administration of protein-rich foods increase the bioavailability of PPPNL HCL by about 50% with no change in time to reach peak concentration, plasma binding, half-life, or the amount of unchanged drug in the urine⁵. An increased frequency of administration is required to achieve desired therapeutic effect. Hence, it was selected as the model drug in the design of buccoadhesive controlled release dosage forms. Deelip Derle et al formulated mucoadhesive bi-layer buccal tablets of propranolol hydrochloride using the bioadhesive polymers such as sodium alginate and carbopol 971 P along with ethyl cellulose as an impermeable backing layer^6-8. The aim of research work is to develop effectious and safe prolonged release mucoadhesive buccal matrix tablets of PPPNL HCl using combined natural and synthetic mucoadhesive polymer for antihypertensive effect. Unidirectional release PPPNL HCl tablets were prepared by direct compression technique with ethyl cellulose as a backing layer to avoid the drug release from the surfaces that are exposed to non-mucosal area.

METHODS AND MATERIALS:

Propranolol hydrochloride (PPPNL HCl) was obtained as gift sample from Zim laboratory, Nagpur. Prunus amygdalus gum was purchased from local market of Amravati district, Maharashtra. Microcrystalline cellulose (MCC) PH-101, Talc, Magnesium Stearate, Acetone, Carbopol 971P and HPMC M4K (AR) were procured from SD Fine Chemicals, Mumbai. All the chemicals and reagents were used of analytical grade.

Isolation and chemical characterization of P. Amygdalus polysaccharide:

The gum of Prunus amygdalus was thoroughly washed and cleaned to remove all the adhered foreign material. It was dissolved in water and reprecipitated using an equal quantity of 95% ethanol. The precipitated polysaccharide was filtered through several folds of muslin cloth, dried at 400C for 2 hr, passed through sieve no. 80 and stored in air tight container for further use. Its purity was tested carrying out tests for the presence of various phytoconstituents. Various general tests are performed like alkaloids, glycosides, carbohydrate, flavonoids, steroids, amino acid, saponins, tannins and phenols^{6, 9}.

Drug-excipient compatibility studies by Fourier Transform Infrared (FTIR):

Pure drug (PPNL HCl), Prunus amygdalus polysaccharide, polymers and their physical mixtures were examined by Fourier Transform Infrared (FT-IR) spectra using potassium bromide pellet method. The FTIR spectra were recorded from 4000 cm-1 to 400 cm-1 in a FTIR Affinity-1(DRS-8000), Shimadzu Japan Spectrophotometer^10-12.

Preparation of unidirectional release Prunus Amygdalus polysaccharide-based buccoadhesive tablets:

Development of unidirectional release buccoadhesive tablets involves preparation of mucoadhesive matrices and coating of the core tablets for backing layer with water impermeable polymer (Fig. 1).

Figure 1: Flow diagram of direct compressible buccoadhesive tablets

Preparation of buccoadhesive core PPNL HCl tablets:

The tablets were prepared by direct compression method using Rimek Minipress rotary tablet machine to obtain the tablets of desired specification. The drug/polymer mixture ratio prepared by homogenously mixing the PPNL HCl with various concentration of polysaccharide and other polymers. According to the formulae presented in Table 1, all the ingredients sufficient for a batch of 100 tablets were weighed and passed through the sieve 40 (420 mm) and mixed by geometric dilution method and finely mixed using polythene bag for proper mixing, then prior compression magnesium stearate and talc was added as lubricating agent and compressed using a 8 mm round concave punches in 10 station tablet punching machine.

Table 1: Formulation of mucoadhesive buccal matrix tablets of PPNL HCl

Ingredients (mg)	Formulation Code
Ingredients (mg)	F1	F2	F3	F4	F5	F6	F7	F8	F9
Propranolol HCl	20	20	20	20	20	20	20	20	20
Prunus amygdalus gum	-	30	15	6.66	10	13.33	16.66	20	23.33
HPMC K4M	-	-	-	6.66	10	13.33	16.66	20	23.33
Carbopol 971P	30	-	15	6.66	10	13.33	16.66	20	23.33
MCC	142	142	142	152	142	132	122	112	102
Mannitol	10	10	10	10	10	10	10	10	10
Magnesium Stearate	3	3	3	3	3	3	3	3	3
Talc	5	5	5	5	5	5	5	5	5

Coating of the core tablet:

Minimum amount of the coating material required for uniform coating of surfaces of core tablet was determined by the trial-and-error method and it was fixed as 50 mg. The backing layer of ethyl cellulose in acetone (6 %w/v) was applied through sprayed on to three side surface of the mucoadhesive tablets leaving the other side free¹³. Then it was air dried at room temperature. The double layered structure design was expected to provide drug delivery in a unidirectional fashion to the mucosa. It avoids loss of drug due to wash out of saliva and the swelling profile of the buccal tablet can be changed dramatically by the amount of backing material and those changes could alter drug release profile. The optimized formulations were obtained by subjecting the evaluation parameters to ANOVA.

Preformulation studies for pre-compression parameters:

Preformulation studies carried out of individual powders for flow properties, bulk density, tapped density, compressibility index and hausner’s ratio¹⁴.

Evaluation of the prepared tablets:

Prepared buccoadhesive tablets were evaluated for physicochemical properties like hardness, friability, thickness, uniformity of weight, drug content uniformity. In-vitro dissolution, buccoadhesion strength, ex-vivo residence time, swelling, and surface pH studies were also performed.

Thickness and diameter:

Thickness and diameter of a tablet were measured using Vernier Callipers (Mutotoya, Japan).

Hardness and Friability¹⁵:

Hardness was measured using Monsanto hardness tester in triplicate. Ten tablets were weighed accurately and placed in the tumbling apparatus that revolves at 25 rpm dropping the tablets through a distance of six inches with each revolution. After 4 min, the tablets were weighed and the percentage loss was determined.

Weight Variation^{15, 16}:

Twenty tablets were randomly selected from each batch and individually weighed. Average weight was calculated from the total weight of all tablets. The individual weights were compared with the average weight. The percentage difference in the weight variation should be within the permissible limits (±7.5%). The percent deviation was calculated using the following formula;

Content uniformity:

Randomly twenty tablets were weighed and powdered. A quantity equivalent to 20 mg of PPNL HCL was placed in 100 mL volumetric flask and dissolved in ethyl alcohol, sonicated for 5 minutes and made up the volume up to the mark and filtered through membrane filter. The filtrate was evaporated and the drug residue dissolved in 100 mL phosphate buffer pH 6.8. The 5 mL solution was then diluted with phosphate buffer pH 6.8 up to 20 mL, filtered through whatman filter paper, and analyzed at 290 nm using a UV Double beam spectrophotometer (Shimadzu, Japan) against suitable blank using standard plot equation⁷.

Surface pH determination of mucoadhesive tablets:

Mucoadhesive buccal tablets were swells for two hours in 1mL of distilled water. The surface ph was measured by pH meter placed on the core surface of the swollen tablet⁷.

In-vitro bioadhesion study^{9, 17}:

Mucoadhesive strength of the buccal tablets is measure by using modified two‐arm physical balance. Goat buccal mucosa was obtained from the local slaughter house, washes with distilled water and then with phosphate buffer pH 6.8 at 370C. The buccal mucosa is cut into pieces and again washes with phosphate buffer pH 6.8. Pieces of buccal mucosa are tied to the glass slide and slide is attached to glass beaker with the cynoacrylate gum.

The glass slide is tightly fit onto a glass beaker and kept into 500 ml beaker (filled with phosphate buffer pH 6.8 at 370C ± 0.50C), so that it just touches the mucosal surface. The buccal tablets are stick to lower side by glass slide attached buccal membrane by cynoacrylate gum. The two side of the balance are made equal before the study, by keeping a weight (5 gm), are removes from the right‐hand pan, which lower the pan along with the tablet over the mucosa. The balance is kept in the position for 1 min contact time. Mucoadhesive strength was assess in terms of weight (gm) required to detach the tablet from the membrane. Mucoadhesive strength which was measured as force of adhesion in Newton’s by using following formula was used.

In-vitro drug dissolution^{10, 18}:

The US Pharmacopoeia XXIII rotating paddle method, 900 mL of phosphate buffer (pH 6.8) as the dissolution medium at 37.0 ± 0.50C and a rotation speed of 50 rpm was used to study drug release from the buccal tablet. One side of the buccal compact was attached to the glass slide with instant adhesive (cyanoacrylate adhesive). The slide was put in the bottom of the dissolution vessel. 5 ml samples from each formulation were withdrawn at 60 minute interval and replaced with fresh medium. The samples were filtered through 0.45-μm whatman filter paper and analyzed using a UV spectrophotometer at 290 nm. The sample was further diluted with corresponding media and absorbance measured in a UV spectrophotometer (Pharma Spec UV- 1700; Shimadzu, Japan) at 290 nm against suitable blank. The absorbance was converted to drug concentration using a calibration curve (Abs = 0.052xConc + 0.045; R2 = 0.999) and then cumulative % drug released was calculated with the help of dilution factor.

Swelling Studies:

Buccal tablets were individually weighed (W_o) and kept separately in small wire basket and then place in a glass beaker with 25 ml of phosphate buffer of pH 6.8. At the time interval of 30 min., 60 min., 90 min., 120 min., 150 min. and 180 min., tablets with basket were removed from the glass beaker and excess water was removed carefully using the filter paper. Then the swollen tablet were reweighed (W_t) and the percentage swelling index was calculated using the following formula¹⁹;

Where, S.I. = swelling index

W_t= average weight of tablet at time t.

W_o = average weight of dry tablet before placing on the phosphate buffer

In-vitro residence time:

The in-vitro residence time was determined using a locally modified USP disintegration apparatus^20-21. The disintegration medium was composed of 800 ml phosphate buffer pH 6.8 maintained at 37 ± 2°C. A goat buccal mucosa, 3 cm length, was glued by cynoacrylate gum to the surface of a glass slide, vertically attached to the apparatus with the help of tag. The mucoadhesive tablet was hydrated from one surface using few drop of phosphate buffer pH 6.8 and then the hydrated surface was brought into contact with the mucosal membrane. The glass slide was vertically fixed to the apparatus and allowed to move up and down so that the tablet was completely immersed in the buffer solution at the lowest point and was out at the highest.

Analysis of in-vitro drug release kinetics and mechanism:

To analyze the drug release from sustained release matrix PPNL HCL formulation, by model dependent approach dissolution data was fitted in to popular models. The drug release data from all batches were fitted in to various kinetic release mathematical models such as zero order, first order, Higuchi, Hixon–Crowell cube root model and Korsmeyer-Peppas models by using PCP-Disso-v3 software. The regression coefficient (r²) value compared to each other and selected best fit model, the release mechanism of PPNL HCl from system were decided from release exponent value^10,22.

Accelerated stability studies:

The optimized matrix buccoadhesive tablets were first wrapped in aluminium foil then placed in an amber colour bottle. Stability studies of the best fit formulation were conducted under accelerated conditions at 40+2ºC/ 75+5% RH for about 6 months in stability chamber (Thermo lab). Samples were collected at 1, 2, 3 and 6 months and analyzed for mucoadhesive strength, mucoadhesive retention time, content uniformity, friability, drug release profile and FTIR spectroscopy.

RESULTS AND DISCUSSION:

Preformulation testing is an investigation of physical and chemical properties of a drug substances alone and when combined with excipients. Physical property of drug and excipient was determined by deferent parameter like angle of repose, bulk density, tapped density, carr’s index and hausner ratio according to above result that was representing in (Table 2). Flow property of Propranolol HCl, Prunus amygdalus gum and MCC was excellent but the flow property of HPMC K4M; carbopol 971P was passable according to USP NF-25, so that all the excipient and drug was good for the preparation of formulation for the direct compressible buccal tablet of propranolol HCl.

Table 2: Physical property of drug and excipients

Physical parameter	Angle of repose	Bulk density	Tapped density	Carr's index	Hausner ratio
Propranolol HCl	25.2	0.847	0.925	8.47	1.09
Prunus amygdalus gum	30.1	0.746	0.833	10.4	1.11
HPMC K4M	45.5	0.322	0.526	38.71	1.63
Carbopol 971P	42.5	0.32	0.432	26.2	1.35
MCC	27.2	0.49	0.588	16.6	1.2

Prunus amygdalus gum was subjected characterization was perform by different phytochemical identification test and was found to absence of alkaloid, flavonoids, steroids, amino acid, saponins, tannins and phenols. The presence of carbohydrate and glycoside shows the basic property of gum.

Compatibility Study:

Fig. 2: FT-IR spectra of The FT-IR spectra of a) propranolol hydrochloride, b) HPMC K4M, c) Carbopol 971P, d) Prunus amygdalus gum and e) their physical mixture

Fourier transform infrared spectra were obtained by using FT-IR Affinity-1 spectrophotometer using KBr disk technique, for determination of drug, polymer and excipients compatibility with each other, (Fig. 2) spectra was of propranolol HCl gives a spectra which gives a confirmation of ortho substitution on benzene ring at 736.81 cm^-1, C-O-C aromatic aliphatic ether, C=C Aromatic ring stretching and R-NH-R stretching were 1112, 1579 and 3319 cm^-1 that spectra gives a clear identification of propranolol hydrochloride.

An individual spectra of HPMC K4M, carbopol 971P, Prunus amygdalus gum have no any peak of NH₂ group but in the physical mixture of propranolol HCl with polymer and excipients shown various peaks at the different wave number 769, 1112, 1579, 3327 and 3600 cm-1 which gives the direct confirmation of propranolol hydrochloride⁹. This shows that there are no considerable changes in the position of characteristic bands associated with drug and individual ingredients, thus there is no interaction between drug-polymer and polymer-polymer.

Post compression parameters of matrix tablets:

Thickness of all the batches formulations ranged from 2.06 mm to 2.26 mm. Hardness of all the batches formulation showed hardness value in the range of to 7.97 to 8.55 kg/cm². In present study, the friability values for all tablet formulation were found to be 0.25% to 0.55%. Less than 1% indicates that the friability within the prescribed limits (Table 3). The pharmacopoeia limits for deviation for tablets of more than 100 mg are ± 10%. The average percentage deviation for all tablets was found in the range of 1.9 to 3.3 %.

Table 3: Post compression parameters of F1 to F9 matrix formulation

Formulation code	Thickness (mm)	Hardness (Kg/cm²)	Friability (%)	Content Uniformity (%)	Surface pH ± SD
F1	2.25±0.07	8.50±0.04	0.51	98.65	6.42±0.12
F2	2.20±0.03	8.35±0.17	0.48	96.0	6.28±0.39
F3	2.22±0.05	8.07±0.15	0.31	97.0	6.38±0.45
F4	2.06±0.05	8.06±0.09	0.40	99.83	6.22±0.35
F5	2.06±0.06	8.34±0.14	0.36	93.23	6.54±0.41
F6	2.19±0.03	8.45±0.07	0.46	98.32	5.78±0.58
F7	2.15±0.05	8.44±0.08	0.48	99.0	5.66±0.24
F8	2.25±0.05	8.07±0.08	0.25	99.85	6.51±0.29
F9	2.26±0.05	7.97±0.06	0.26	99.78	6.23±0.28

Friability, uniformity of weight, and drug content uniformity were within the limits as per the Indian Pharmacopoeia (IP). The results indicate of all the formulation was found to be within the specified limits and hence all formulation complied with official limit. Uniformity of drug content was found within and among the different batches of tablet formulation. The value ranged from 93.23% to 99.85%. The surface pH of the tablets was determined to investigate the possibility of any side effects, on the oral cavity. As acidic or alkaline pH was found to cause irritation to the buccal mucosa, hence attempt was made to maintain surface pH close to the neutral pH. Tablets of all the batches have shown a surface pH in the range of 5.66-6.54 that indicates no risk of mucosal damage or irritation because all batches formulation shows pH in the range of oral mucosa pH.

In-vitro mucoadhesive study:

Results of the mucoadhesive properties of the prepared formulations are shown in Fig.3. Mucoadhesive strength and ex-vivo residence time of the formulations were found be in the range of 14.4 –18.2 gm and 4.50–8 hrs, respectively. While the maximum mucoadhesive strength 18.2 gm and ex-vivo residence time of 8 h were observed for the formulation F8 containing drug to BG in the ratio of 1:1 gives satisfactory strength and excellent result.

Fig. 3: In-vitro mucoadhesive strength, mucoadhesive force and mucoadhesive retention time of F1 to F9

Swelling Index profile:

All the prepared formulations were evaluated for their swelling ability. Swelling index was measured up to 5 hrs (Fig.4). Swelling index values were found to be increased with the increase in concentration of Prunus amygdalus gum and carbopol. From the obtained results, it can be concluded that mucoadhesive property of Prunus amygdalus gum and polymers is directly proportional to its concentration in the formulations. Formulation F2 shows highest swelling property were F3, F4, F5, F6, F7, F8, F9 also shows good swelling property but formula F1 shows less swelling property due to absence of Prunus amygdalus gum in that formulation.

In-vitro drug release:

In-vitro dissolution studies were performed in pH 6.8 phosphate buffer and dissolution profiles are shown in Fig.5. From the dissolution studies, it was observed that as the concentration of Prunus amygdalus gum increases drug release was prolonged indicating the drug release retarding ability of the Prunus amygdalus gum. Burst release was observed for the formulations containing microcrystalline cellulose (MCC) as diluents as they released 100% of drug within 5 hrs. This might be due to the elastic nature of the MCC which hinder the release of highly soluble drug from the matrix tablet resulting in the development of excess pressure in tablet as tablet was coated with impermeable cellulose acetate layer on three sides where there is less/no chance for the drug release. From the above observations, formulation F8 containing drug to Prunus amygdalus gum in the ratio of 1:1 and synthetic polymers to extended the drug release up to 5 h and was considered as preliminary optimized formulation.

Fig. 4 : Swelling profile of formulation F1 to F9

Fig. 5: Dissolution profiles of Prunus amygdalus gum-PPNL HCl buccoadhesive tablets

Table 4: In-vitro drug release kinetic data of mucoadhesive buccal tablet of F1 to F9

Formulation codes	Zero order	First order	Matrix	Hixon Crowell	Korsmeyer-Peppas		Best Fit Model
Formulation codes	R2	R2	R2	R2	R2	Release exponent (n)	Best Fit Model
F1	-	-	-	-	-	-	None
F2	0.9734	0.9744	0.9104	0.9741	0.9749	1.3326	Peppas
F3	0.9738	0.8718	0.9056	0.9185	0.9487	0.7714	Zero order
F4	0.9379	0.826	0.8779	0.8745	0.8805	0.6486	Zero order
F5	0.9216	0.9222	0.9477	0.9289	0.931	0.5156	Matrix
F6	0.9018	0.9553	0.9807	0.9415	0.9237	0.4402	Matrix
F7	0.8937	0.9535	0.9821	0.9381	0.9228	0.416	Matrix
F8	0.9582	0.9466	0.9371	0.9573	0.9019	0.5852	Zero order
F9	0.9129	0.9404	0.9601	0.9437	0.8883	0.433	Matrix

Fig. 6: Dissolution profiles of formulation F8 and marketed product

All formulation batches F1 to F9 were subjected to various release models, by using PCP-Disso-v3 software. The formulation F1 does not fit in any models were formulation F2 fit in peppas kinetic model, F3, F4 and F8 fit in zero order kinetic model and F5, F6, F7, F9 fitted in matrix type kinetic model that the value were reported in Table 4.

By using Korsmeyer and peppas equation the release exponent (n) value were obtained in range of 0.416 to 1.332 for all formulation. By using the value of ‘n’ easily found the diffusion mechanism of all the formulation were formulation F2 shows super case 2 diffusion while F3, F4, F5 and F8 shows non-fickian diffusion and F6, F7, F9 shows fickian diffusion mechanism. From overall results of all formulation , the formulation F8 was the best formulation from other formulation, that conclusion are easily detected on basis of the result of mucoadhesion study, in-vitro residence time, drug content uniformity, friability and percentage drug released shows zero order kinetic. In-vitro drug dissolution compared of optimized formulation F8 with marketed formulation. Marketed formulation was rapidly dissolved in dissolution media it doesn’t give controlled release as compared to F8 formulation (Fig. 6).

The optimized formulation F8 showed no significant change in in-vitro release profile, drug content, hardness, weight variation and mucoadhesivity and found that the formulation was a stable one at 40°C/75% RH for 6 months. The formulation of buccal tablet of PPPNL HCl will be provide a controlled release pattern with the addition of mucoadhesive material like HPMC K4M, Carbopol 971P, Prunus amygdalus gum are help to make a controlled release and solve all that problem of like bioavailability, hepatic first pass and half life of drugs. The formulation F8 was the best formulation from other one formulation; it was easily detected on basis of the result of mucoadhesion study, in vitro residence time, drug content uniformity, friability and percentage drug released. The mechanism of release of propranolol HCl from matrices was following zero order as well as non-fickian diffusion.

CONCLUSIONS:

Matrix buccoadhesive tablets of propranolol hydrochloride prepared with combination of 20% of each Prunus amygdalus gum, HPMC K4M and Carbopol 971P was found good physical properties and retarded the drug release effectively for 5 hrs. From the present study, it can be concluded that propranolol HCl matrices could be developed with desirable release modulation for buccoadhesive administration.

ACKNOWLEDGEMENT:

Authors are thankful to Zim Laboratories limited, Nagpur for donating gift sample of propranolol HCl and to the Principal, Government College of Pharmacy providing necessary facilities to carry out this work.

CONFLICT OF INTEREST:

Author(s) are declared that no the conflict of interest.

REFERENCES:

1. Boyapally H, Nukala RK, Bhujbal P and Douroumis D. Controlled release from directly compressible theophylline buccal tablets. Colloids and Surfaces B: Biointerfaces. 2010; 77(2):227-233.

2. Ikinci G et al. Development of a buccal bioadhesive nicotine tablet formulation for smoking cessation. International journal of pharmaceutics. 2004; 277(1): 173-178.

3. Shojaei AH. Buccal mucosa as a route for systemic drug delivery: a review. J Pharm Sci. 1998; 1(1):15-30.

4. Srikrishna T et al. Design, Development and Evaluation of Buccal Tablets of Pregabalin. Research J. Pharm. and Tech. 2017; 10(2):579-588.

5. Srikanth MV et al. Statistical design and evaluation of a propranolol HCl gastric floating tablet. Acta Pharmaceutica Sinica B. 2012; 2(1):60-69.

6. Meka VS, Nali SR, Songa AS and Kolapalli VR. Characterization and in vitro drug release studies of a natural polysaccharide Terminalia catappa gum (Badam gum). AAPS Pharm Sci Tech. 2012; 13(4): 1451-1464.

7. Prasanth BA et al. Effect of moringa gum in enhancing buccal drug delivery of propranolol hydrochloride. International journal of research in pharmacy and chemistr. 2011; 1(2):111-116.

8. Derle D et al. Formulation and evaluation of buccoadhesive bi-layer tablet of propranolol hydrochloride. International journal of pharmacy and Pharmaceutical Sciences. 2009; 1(1):206-212.

9. Harikrishnan V, Madhusudhan S and Santhiagu A. Evaluation of a Novel, Natural Badam Gum as a Sustained Release and Mucoadhesive Component of Tizanidine HCl Buccal Tablets. Asian J. Pharm. Tech. 2015; 5(2):71-78.

10. Shende MA and Marathe RP. Development and Optimization of Oral Gastroadhesive Matrices for Diltiazem Hydrochloride Using Some Natural Materials. Research J. Pharm. and Tech. 2016; 9(7):831-834.

11. Kumar P and Kulkarni GT. Characterization of mucilage from artocarpus heterophyllus as pharmaceutical excipient. Journal of Chronotherapy and Drug Delivery. 2013; 4(1):31-43.

12. Coates J. Interpretation of Infrared Spectra, a Practical Approach. John Wiley and Sons Ltd, Chichester, Meyers RA, editors. Encyclopedia of Analytical Chemistry. 2000; pp. 10815–10837.

13. Wadageri GV, Raju SA, Shirsand SB and Reddy VP. Buccal Drug Delivery System of Atenolol. Research J. Pharm. and Tech. 2012; 5(7): 894-900.

14. Nikam AP and Ratnaparkhi MP. Formulation and Evaluation of Losartan Potassium Sustained Release tablets. Research J. Pharm. and Tech. 2014; 7(11):1219-1225.

15. Lachman L, Lieberman HA, Kanig JL. The theory and practice of industrial pharmacy. Philadelphia: Lea and Febiger; Varghese Publishing House. 1990; 3rd Ed: pp. 199,329-335.

16. Deshmukh VN and Sakarkar DM. Development and Evaluation of Controlled Release Mucoadhesive Tablet. Research J. Pharm. and Tech. 2011; 4(4):578-581.

17. Patel VM, Prajapati BG and Patel MM. Formulation, evaluation, and comparison of bilayered and multilayered mucoadhesive buccal devices of propranolol hydrochloride. Aaps Pharmscitech. 2007; 8(1):E147-E154.

18. Bhanja S et al. Formulation and in-vitro evaluation of mucoadhesive buccal tablets of Timolol maleate. Int J Pharm Biomed Res. 2010; 1(4):129-134.

19. Kotadiya R, Patel V and Patel H. Hydrophilic Matrices Geometry, Swelling and Erosion Investigations to Clarify the Release Mechanism. Research J. Pharma. Dosage Forms and Tech. 2009; 1(3):191-195.

20. Nakamura F et al. In vitro and in vivo nasal mucoadhesion of some water-soluble polymers. International journal of pharmaceutics. 1996; 134(1-2):173-181.

21. Sirisha Y and Venkateswara Rao T. Formulation and Evaluation of Bilayered Buccal Adhesive Tablets of Carvedilol. Research J. Science and Tech. 2011; 3(6): 335-339.

22. Ravi Kumar V et al. Improvement of dissolution characteristics and bioavailability of tadalafil by solid dispersion technique using water soluble polymer. International Journal of Advanced Pharmaceuti. 2012; 2(2):56-63.

23. Patial JS. A Review on Stability and Instability in Fluids and Solids. Research J. Engineering and Tech.2012; 3(2): 171-175.

Received on 28.08.2017 Accepted on 19.10.2017

Asian J. Pharm. Tech. 2017; 7 (4): 181-188 .

DOI: 10.5958/2231-5713.2017.00029.0