1. INTRODUCTION:

The goal of any drug delivery system is to provide a therapeutic amount of drug to the required action site in the body, to achieve and maintain therapeutic concentration within the therapeutic range and to show optimal pharmacological action with minimum incidence of adverse effects. In order to achieve the said goal, a precise dosing frequency and a suitable route of administration should be decided upon^[1]. Gastro retentive drug delivery is an approach to prolong the gastric residence time of drugs, there by targeting site specific drug release in the upper GIT for local and systemic effects.

Gastro retentive drug delivery systems can be used to significantly enhance the bioavailability of therapeutic agents which tend to get metabolized predominately in the upper GIT. In addition, this approach can also be used to reduce the dosing frequency of drugs that possess a relatively shorter half-life thereby providing a sustained release with minimal fluctuations in plasma drug concentration. Drugs which are unstable in the intestinal environment can be delivered in the stomach by gastroretension approaches^[2]

There are various approaches that could be employed to provide gastric retention namely: low density system (floating dosage forms), effervescent systems, swelling systems, high density systems, mucoadhesive systems, super porous hydrogels, expandable systems and magnetic systems.

Hypertension is a common disease in industrialized countries and accounts for a major cause of death worldwide. Oral delivery of anti-hypertensive dugs is the preferred route for drug administration as it is more natural and less invasive than other available routes. This is in turn increases patient compliance and assures safety than the other invasive routes.

Captopril, a potent ACE inhibitor which is widely used in the treatment of hypertension when given orally is absorbed rapidly and has a bioavailability of 75%, ahalf-life of 2-3 hours andpeak plasma concentrations occur within an hour. Captopril is freely soluble in water and has site specific absorption from GIT and on the other hand, the drug is unstable in the alkaline pH and specifically absorbed from stomach^[4]. Oral bio adhesive systems offer the promise of prolonged luminal release with improved localized delivery and increased absorption of therapeutic agents. The gastro retentive mucoadhesive patch systems binds to mucin molecules in the mucous lining and is therefore retained on the surface epithelium for extended periods of time thereby increasing the GI transit time and the mean residence time of the drug. Improvement in the mean residence time increases the extent of absorption. Stability problems of the drugs in the intestinal fluids can be overcomed by the application of gastro retentive mucoadhesive patches as it will be retained into the stomach.^[3] These advantages of gastro retentive mucoadhesive patches initiate the focus of this research to formulate a bilayered gastric mucoadhesive patch of Captopril.

2. MATERIAL AND METHODS:

Materials used for the research work were either AR/LR grade or the best possible pharma grade available supplied by the manufacturer. Captopril (AR) was obtained as a generous gift sample from Unicure Remedies Pvt. Ltd., Gujarat. Chitosan (LR) was obtained from Hi-media Lab Pvt. Ltd., Mumbai. Hydroxy propyl methyl cellulose K-15 (LR) was obtained from Colorcon Asia Pvt., Goa. Hydroxy propyl methyl cellulose E-15 (LR) was obtained from Colorcon Asia Pvt., Goa. Ethyl cellulose (LR) was supplied by S.D. Fine Chemicals Ltd., Mumbai. All other materials were reagent grade and used without further modification.

3. PREFORMULATION STUDIES:

Preformulation studies were performed on the drug which included physicochemical evaluation of the drug and compatibility studies of drug and excipients.

3.1 Physical properties of drug:

The drug was checked for its physical appearance i.e. colour, odour, taste and form. It was also tested for its other physical properties like pH, solubility in different solvents, light and heat stability.

3.2 Determination of melting point:

Melting point of captopril was determined by capillary tube method using Thiel’s tube apparatus. The presence of relatively small amount of impurity can be detected by lowering as well as widening in the melting point range, which was then compared to the standard melting point values.

3.3 FT-IR spectroscopy:

The FT-IR spectrum helps to confirm the identity of drug and to detect any possible interaction of drug with the carriers. IR spectroscopy of pure drug and a physical mixture of drug with polymers were carried out using shimadzu FT-IR, carried out by the KBr pellet method. The IR spectra of drug with polymers were compared with standard IR spectrum of pure drug.

3.4 Compatibility study:

The compatibility studies of the drug and polymers were carried out by preparing a physical mixture of drug and polymer in 1:1 ratio. The mixture was kept at room temperature for one month. These samples were periodically examined for physical changes. Drug content and FT-IR studies were carried out after one month.

4. FORMULATION:

4.1 Preparation of backing membrane:

Patches were casted by solvent casting technique. For the preparation of backing membrane, ethyl cellulose (EC) was dissolved in acetone and dibutyl phthalate was added to the polymeric solution. The resultant mixture was poured into a Petri dish, 60.845cm² in area, and kept for controlled drying under an inverted funnel. Various concentrations of polymer and dibutyl phthalate were used to optimize the preparation of patches. Folding endurance and thickness were considered for optimization.

Table 4.1: Composition of backing membrane

	BF1	BF2	BF3	BF4	BF5	BF6	BF7	BF8	BF9
Ethyl cellulose	10%	7.5%	5%	10%	7.5%	5%	10%	7.5%	5%
Dibutyl phthalate	25%	25%	25%	30%	30%	30%	50%	50%	50%

4.2 Preparation of mucoadhesive layer:

a. Selection of polymer:

For the preparation of mucoadhesive layer, different polymers in different concentrations were used. Mucoadhesive films were prepared by solvent casting method using Chitosan, HPMC K-15, Pectin, sodium carboxy methyl cellulose and sodium alginate as mucoadhesive and film forming polymers. However, based upon physical characteristics and retention time, chitosan and HPMC K15 were used as mucoadhesive and film forming polymer respectively. For optimizing the concentration of mucoadhesive polymer, a 3²general factorial design was applied, table 4.2.

b. Factorial design:

The two independent variables such as Chitosan (X1) and HPMC (X2) were chosen on the basis of preliminary trials which were carried before as mentioned above. Effects of independent variables like concentration of Chitosan and HPMC K15 on the mucoadhesive layer were evaluated. Folding endurance, mucoadhesive strength, mucoadhesion time and in-vitro drug release at 12 hours were selected as dependent variable.

Table 4.2: Amount of variables in 3²general factorial design.

Coded Values	Actual Values (%)
	X₁	X₂
-1	1	0.5
0	1.5	0.75
+1	2	1.5

The mucoadhesive patches containing Captopril were prepared by solvent casting method, table 4.3. Specified amount of Chitosan was separately soaked and stirred for 24 hours in 2% v/v acetic acid. To this specified amount of HPMC K15 was added. Required quantity of drug was then dissolved into the polymeric solution. Propylene glycol was used as plasticizer. The drug-polymeric solution was spread on the backing membrane and air dried.

Table 4.3: Formulation as per 3²general factorial design

Ingredients	F1	F2	F3	F4	F5	F6	F7	F8	F9
Captopril (mg)	50	50	50	50	50	50	50	50	50
Chitosan (%)	1	1	1	1.5	1.5	1.5	2	2	2
HPMC K15 (%)	0.5	0.75	1.5	0.5	0.75	1.5	0.5	0.75	1.5
Propylene glycol (ml)	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5

4.3 Preparation of immediate release layer:

Immediate release layer was prepared using different polymer such as polyvinyl alcohol and HPMC E-15 in different concentrations as shown in table 4.4.

Table 4.4: Selection of immediate release polymer

Formulation code	Polymer	Concentration (%w/w)	Plasticizer (ml)
IF1	Polyvinyl alcohol	15	0.75
IF2	HPMC E15	1.25	0.5
IF3	HPMC E15	2.5	0.5
IF4	HPMC E15	5	0.5

Required amount of polymer was soaked in sufficient amount of water for 12 hours and stirred on a magnetic stirrer, table 4.4. Drug was then uniformly dispersed into the polymeric solution. Propylene glycol was added as plasticizer and stirred till the drug was dissolved. The prepared solution was then casted on the mucoadhesive layer and air dried. 12.5 mg of drug was added as initial dose in immediate release layer

5 EVALUATION PARAMETERS:

5.1 Physical characteristics study:

All patches were visually inspected for colour, clarity, flexibility and smoothness.

5.2 Uniformity of weight of patch:

Patches of (2x3cm) were taken from different positions of the patch and average was calculated. The weight variation of each patch was calculated.

5.3 Thickness of patches:

The thickness of the polymer films (3x2cm) was determined by using a micrometer screw gauge. The thickness of each strip at six different places was determined and standard deviation was calculated.

5.4 Folding endurance:

Folding endurance was determined by repeatedly folding the patch at the same place till the patch broke or folded^[6,7].

5.5 Drug content uniformity

Drug content uniformity was determined by dissolving the patch (3x2 cm) from each formulation in 0.1 N HCl. The resulting solution was filtered through a whatman filter paper. The drug content was then determined after appropriate dilutions at 201 nm using a UV spectro photometer^[8,9].

5.6 Unfolding study:

The unfolding study of the bilayered patch was conducted using USP Type–I dissolution apparatus

The capsule was placed in the basket, immersed into 0.1N HCl. The capsule dissolved and then the unfolding of the inner patch was observed^[15,11].

5.7 Swelling index:

The swelling behavior of the sustain release layer was evaluated by initially taking the dry weight of the sustained release layer which was then kept in 100 ml of water. After 5 minutes the film was taken out and excess amount of water was removed using a blotting paper and weighed. Repeat the same procedure for 10, 15, 30 and 60 minutes^[11].

Swelling index=[(final weight – initial weight)÷final weight]* 100

5.8 Ex-vivo mucoadhesion strength:

Fresh goat mucosa was obtained from a local slaughter house, and placed in saline, and used within 2 hours of slaughter. The mucosal membrane was cleaned and separated from underlying fat layer. Mucoadhesive strength of the film was measured by using a modified physical balance.

The device was mainly composed of a two arm balance. The left arm of balance was replaced by a small plastic cup vertically suspended through a wire. At the same side, a beaker was placed containing a glass tube which was tightly fitted at the bottom of the beaker. The mucosa was tied to the open end of the glass tube. The glass beaker was filled with 0.1N HCl in such a way that it makes contact with gastric mucosal surface.

The mucoadhesive layer was stuck to the lower side of the flat pan with cyanoacrylate glue. Two pans of the balance were balanced with 5g weight on the right hand side pan. A weight of 5g was removed from right hand side pan which in turn lowered the pan along with the patch over the mucosa. The balance was kept in the position for a 5 minutes’ contact time, and then slowly the weights were increased on the right hand side pan till the patch separated from the mucosal surface^{[15,11,12,13]}.

5.9 Ex-vivo mucoadhesion time:

Mucoadhesion time was determined by using the USP disintegration apparatus. The fresh goat mucosa 3cm in length was attached to the glass slide using cyanoacrylate glue. Mucoadhesive layer was then attached to the mucosa. The glass slide was vertically suspended into the flask containing 800ml of 0.1N HCl maintained at 37±5˚C. The glass slide was allowed to move up and down so that the patch was completely immersed in the buffer solution at the lowest point and was out at the highest point. The time consumed for complete erosion or detachment of the patch from the surface was recorded^[14,16].

5.10 In –vitro dissolution studies:

Dissolution studies were carried out for all formulations, employing USP Type I apparatusat 37±5˚C rotated at speed 50 rpm using 900ml of 0.1 N HCl as dissolution medium. A sample of 2x3 cm patch was used in each test. An aliquot of sample was periodically withdrawn at suitable time interval and the volumes were replaced with fresh dissolution medium in order to maintain sink conditions. The sample was analyzed spectro photometrically^[15,5,11].

5.11 Kinetic analysis:

Kinetic analysis of the in vitro dissolution profile of optimized formulations was fitted into kinetic models like zero order release, first order release, higuchi, korsemeyar-peppas to estimate the order of drug release.

5.12 Stability studies:

Patches were subjected to accelerated stability testing. Patches wrapped in aluminum foil were kept in stability chamber maintained at 40±2˚C and 75 ± 5% RH for 3 months. Changes in appearance and drug content of the stored patches were noted^{[17, 18, 9]}.

6 RESULTS:

6.1 Preformulation studies:

6.1.1 Physical characteristics of drug:

Captopril is a white to off-white crystalline powder with a slight mercaptonodour. It is freely soluble in water, methanol, ethanol, isopropanol and chloroform.

6.1.2 Determination of melting point:

The melting point of Captopril was found to be in the range of 105.2˚C–105.9˚C, which complies to the reported melting point of the drug in official books, hence indicating the purity of drug sample.

6.1.3 FT-IR spectroscopy

The FT-IR spectrum of pure drug was found to be identical with the standard spectra given in Indian Pharmacopeia. Characteristic peaks of Captopril were present in the spectra at respective wavelength indicating purity of same.

Figure 6.1: FT-IR Spectra of Captopril

6.1.4 Compatibility studies:

Compatibility studies of drug and polymer was carried out as mentioned in 3.4, compatibility studies.

Following are the results for drug content, physical appearance and FT-IR.

· In physical appearance it was seen that there was no change at the end of one month.

· FT-IR spectra of drug-excipient was compared with initial FT-IR spectra’s and was seen that characteristic drug peak was present and unaffected.

· Drug content at the end of one month showed no significant change.

Table 6.1: Drug-polymer compatibility study

]	Mixture	Physical appearance		Drug content
]	Mixture	Day 1	Day 30	Day 1	Day 30
1	Captopril + EC	No change	No change	98.2%	97.9%
2	Captopril + HPMC E15	No change	No change	98.1%	97.6%
3	Captopril + Chitosan	No change	No change	97.5%	97.1%
4	Drug + HPMC K15	No change	No change	97.6%	97.0%
5	Captopril + Chitosan + HPMC K15	No change	No change	98.1%	97.9%
6	Captopril + Chitosan + HPMC K15 + HPMC E15	No change	No change	98.4%	97.3%

Figure 6.2: FT-IR Spectra of Captopril+Ethyl cellulose

Figure 6.3: FT-IR Spectra of Captopril + HPMC E15

Figure 6.4: FT-IR Spectra of Captopril + Chitosan

Figure 6.5: FT-IR Spectra of Captopril + HPMC K15

Figure 6.6: FT-IR Spectra of Captopril + Chitosan + HPMC K15

Figure 6.7: FT-IR Spectra of Captopril+Chitosan+HPMC K15+HPMC E15

From the results above, it was concluded that the selected polymers were compatible with the drug and could be accepted as drug and polymer of choice for further required formulation.

6.2 Formulation:

The bilayered gastric mucoadhesive patch was successfully formulated. It consists of three layers: immediate release layer, mucoadhesive layer and backing membrane.

6.2.1 Preparation of backing membrane:

Formulation of the backing layer was as per 4.1. Different concentrations of ethyl cellulose and dibutyl phthalate were used.

Table 6.2: Optimization of backing membrane formulation

Formulation Code	Thickness	Flexibility
BF1, BF4, BF7	Maximum	Minimum
BF2, BF5, BF8	Optimal	Lacked
BF3, BF6, BF9	Optimal	Optimal

BF9 showed best flexibility and hence was selected for final patch.

6.2.2 Preparation of mucoadhesive layer:

Selection of polymer: the different polymers used are mentioned in 4.2. It was seen that mucoadhesive films containing chitosan and HPMC K15 showed highest retention time as well as better physical characteristics such as thickness and flexibility.

Factorial design: the two independent variables selected were chitosan (X1) and HPMC K15 (X2). The concentrations of polymer were selected as per table 4.2 at three levels. The mucoadhesive layer was formulated using 3² general factorial designs. All the nine formulation were then evaluated.

6.2.3 Preparation of immediate release layer:

The immediate release layer was prepared using different polymers as shown in table 4.4.The results of which are shown in table 6.3.

Table 6.3: Optimization of immediate release layer for final formulation

Formulation Code	Disintegration Time
IF1	45 mins
IF2	45 seconds
IF3	1 min
IF4	5 mins

As IF 4 showed optimal disintegration time of 5 minutes and minimum thickness, it was selected for final formulation. The final formulation composed of the three layers of dimensions 2x3 cm were sandwiched together to formulate a compressed patch system, which was encapsulated into a hard gelatin capsule.

Figure: 6.8: Bilayered patch

Figure 6.9: Compressed bilayered patch in a capsule

6.3 Evaluation Parameters:

6.3.1 Physical characteristics study:

The prepared bilayered patch of Captopril was found to be pale yellow in color and opaque. The patches were found to be smooth without any scratches. The pale yellow color was mainly because of the presence of Chitosan.

6.3.2 Uniformity of weight:

The weight of the patches was found to be in the range of 348.267±0.642 mg to 420.167±0.153 mg from F1 to F9 formulations. The average weight of the individual formulations is given in table 6.4.

6.3.3 Thickness of patches:

The thickness of the patch ranged from 0.362 ± 0.0054 mm to 0.374±0.0022 mm from F1 to F9. The average thickness value of all the patches prepared is given in table 6.4.

6.3.4 Folding endurance:

The folding endurance values of the patch from all formulations are given in table 6.4. Folding endurance was found to be in the range of 309±0.58 to 332±0.421folds.

6.3.5 Drug Content:

The drug contents of all the individual formulations are given in table 6.4. Drug content ranges from 95.64% to 98.80%.

6.3.6 In-vitro unfolding study:

The results of in-vitro unfolding study are depicted in Figure 6.10.

Figure 6.10: In-vitro swelling study

6.3.7 Swelling Index:

The swelling indexes of the patches are shown in table 6.5. The percent swelling index ranged from 32.99% to 49.72%.

Table 6.5: Percent swelling of films

Formulation	Percent swelling index in time (minutes)
Formulation	5	10	15	30	60
F1	4.40%	12.05%	21.97%	29.06%	32.99%
F2	6.61%	13.94%	27.70%	32.87%	45.98%
F3	6.82%	15.79%	29.19%	35.59%	52.67%
F4	5.71%	14.58%	25.31%	35.36%	41.66%
F5	6.27%	15.87%	26.93%	32.80%	49.72%
F6	7.65%	18.63%	28.88%	35.97%	56.21%
F7	5.64%	16.26%	23.99%	28.50%	31.82%
F8	6.20%	19.11%	26.69%	31.22%	46.52%
F9	7.81%	21.09%	27.82%	33.36%	49.64%

Figure 6.11: Percent swelling

6.3.8 Ex-vivo mucoadhesion strength:

Mucoadhesive strengths of all nine formulations are depicted in table 6.4.

Figure 6.12: Ex-vivo mucoadhesion strength

Figure 6.13: Measurement of mucoadhesion strength using Modified Analytical Balance

6.3.9 Ex-vivo mucoadhesion time:

The results of the ex-vivo mucoadhesion time of the formulations are depicted in table 6.6. The mucoadhesion time ranged from 7.08±0.46 hours to 10.56±0.21 hours

Table 6.6: Ex-vivo mucoadhesion time

Formulations	*Ex-vitro* mucoadhesion time (n=3) Mean ± SD (hours)
F1	7.08 ± 0.46
F2	7.13 ± 0.49
F3	8.10 ± 0.1
F4	8.73 ± 0.66
F5	9.95 ± 0.39
F6	10.11 ± 0.37
F7	10.30 ± 0.11
F8	10.56 ± 0.21
F9	10.20 ± 011

6.3.10 In-vitro drug release:

The graph of percent cumulative drug release v/s time is shown in Figure 6.14.

Figure: 6.14: Percent cumulative drug release v/s time

6.3.11 Kinetic analysis:

Kinetic analysis of in-vitro dissolution profile of formulations F7 to F9 that prolonged the in-vitro residence time up to 12 hours was carried out in order to estimate the order of drug release. The dissolution profile of F7, F8 and F9 were fitted into kinetic model like zero order release, first order release, higuchi, korsemeyar-peppas. The results of the model fitting are summarized in table 6.7.

Figure: 6.15:Percent cumulative drug release v/s time (zero order model)

Figure: 6.16: Log percent drug remaining v/s time (first order model)

Figure: 6.17: Percent CDR v/s square root of time (Higuchi order model)

Figure: 6.18: log percent CDR versus log time (Peppas model)

Table 6.7: Release kinetics

Formulations	Zero order model	First order model	Higuchi model	Korsmeyer – peppas model
Formulations	Zero order model	First order model	Higuchi model	R²	N
245F7	0.9734	0.883	0.9276	0.8382	0.6459
F8	0.9805	0.9183	0.9216	0.8619	0.7005
F9	0.9799	0.9088	0.9222	0.8444	0.6739

6.3.12 Stability studies:

Patches that were placed in humidity chamber for stability studies were analyzed for appearance, texture and drug content. Drug content retained in the patch was to an extent of 80.05%. It was found that drug loss was less though the patches were stored for one month. The texture and appearance turned little rough due to reduced plasticizing property of the patches though no significant changes were seen.

7 DISCUSSION:

7.1 Evaluation Parameters:

7.1.1 Uniformity of weight:

As per the determined weights of patches shown in table 6.4, it was seen that there was an increase in the weight of each patch of the respective formulation which was mainly attributed to the increase in the polymer concentration.

7.1.2 Thickness of patches:

It was seen that as the concentration of polymers increases, there was a slight increase in the thickness of the patch. Formulation F1 had the least thickness of 0.362±0.0054 mm as the concentration of chitosan and HPMC K15 was less, while F9 had the maximum thickness of 0.374±0.0022 mm as the HPMC K15 and chitosan concentration was high.

7.1.3 Folding endurance:

As per the obtained data, it could be concluded that the films had good mechanical strength and flexibility. As the concentration of the polymer increased, the folding endurance was also found to increase.

7.1.4 Drug content:

The results of drug content uniformity of the patches were within range thus indicating that the drug was uniformly dispersed throughout the patches. All were found to be in acceptable range however F6 showed maximum drug content of 98.8%.

7.1.5 In-vitro unfolding study:

In the in-vitro unfolding study, the capsule dissolved within few minutes and the dissolution of the immediate release layer occurred. The behavior of formulated bilayered patch showed satisfactory results, the mucoadhesive layer swelled and the film unfolded in an acceptable manner. After complete dissolution of the immediate release layer, the patch completely unfolded. This property of the patch aided for its adherence to the gastric mucosal membrane. The problem of unfolding aroused mainly due to reduction in the resilience of the patch to restore to its original shape (its mechanical shape memory) after prolonged stress applied during its storage.

7.1.6 Swelling index:

The results showed that as the concentration of HPMC K15 and chitosan increased, the percent swelling also showed a parallel increase. However, on further increase in concentration of chitosan, percent swelling decreased. Lowest amount of percent swelling was seen in F1 and highest percent swelling was seen in F6. This is mainly attributed to the hydrophilic nature of HPMC K15 that the swelling index increased with increase in its amount. In addition, due to the poor aqueous solubility of chitosan, further increase in the amount of chitosan would reduce the swelling extent.

7.1.7 Ex-vivo mucoadhesion strength:

The strength of the mucoadhesive layer was dependent on the property of mucoadhesive polymers which adheres to the mucosa and also on the concentration of the polymers used. The mucoadhesive layer was prepared by using different concentrations of mucoadhesive polymers such as chitosan and HPMC K15. Among the nine formulations, F8 showed higher mucoadhesive strength of 23.23±0.252 g and F1 showed lowest mucoadhesive strength of 13.13±0.153 g. It was observed that the mucoadhesion strength of the formulations increased with an increase in polymer concentration. The chitosan base has good mucoadhesion strength forming capacity with mucin. As the concentration of chitosan and HPMC K15 increases the mucoadhesion strength increases. However on further increase in chitosan and HPMC K15 the mucoadhesion strength decreased, possibly due to the hydrophilic nature of HPMC K15 which loosened the bond with mucosa.

7.1.8 Ex-vivo mucoadhesion time:

Formulation F1 showed minimum mucoadhesion time of 7.08±0.46 hours. F1 had the least amount of HPMC K15 as well as chitosan, thus the patch was attached to the mucosa for shorter periods of time. The patch was eroded hence the patch was detached from the mucosa. Formulation F8 showed highest mucoadhesion time of 10.56±0.21 hours. This was due to the high concentration of HPMC K15 and chitosan. As the concentration of the polymers were more, the bond between the mucosa and patch was retained for a higher time. It was also seen, as the concentration of the polymer further increased there was no subsequent increase in the mucoadhesion time. The mucosa-mucoadhesive bond of the patch was weak and thus the patch was detached from the mucosa possibly be due to the hydrophilic nature of the polymers.

7.1.9 In-vitro drug release:

Drug release studies were carried out in 0.1 N HCl for 12 hours. As per the results obtained, F1 and F2 formulations, showed percent drug release 96.17% and 95.05% for 8 and 10 hours respectively. This was basically due to minimum concentration of the polymers.

F3 showed drug release of 98.41 % for 11 hours. This was due to highest amount of HPMC K15, thus retention time of the patch also increased. F4 and F5 showed 94.77% and 92.52% drug release upto 11 hours. As the concentration of the chitosan and HPMC K15 increased, the retention time increased subsequently decreasing the drug release.

In case of F7, F8 and F9, the cumulative drug release was 94.21%, 96.73% and 95.89% respectively after 12 hours. It was seen that as the concentration of chitosan and HPMC K15 increases, the cumulative drug release decreases and retention time increases. Increase in the concentration of chitosan and HPMC K 15 prolongs the drug release. The polymer concentration is a major factor affecting the drug release from the mucoadhesive patch.

7.1.10 Kinetic analysis:

The results indicated among all fitted models, the best model was zero order, based upon R²value (0.9805), which suggested that linearity of curve was good and best fitted to zero order model for F7, F8 and F9 formulations. The n value of all three formulations i.e. F7, F8 and F8 was found to be 0.3441, 0.3546 and 0.3518 which is below 0.45 thus corresponding to non-fickian diffusion.

8 ACKNOWLEDGEMENTS:

Sincere gratitude to UnicureRemdies Pvt. Ltd, Gujarat and Colorcon Asia Pvt, Goa for providing gift samples of Captopril and HPMC K15, E15 respectively.

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Received on 29.11.2017 Modified on 21.12.2017

Research J. Pharm. and Tech 2018; 11(6): 2444-2453.

DOI: 10.5958/0974-360X.2018.00451.1

Formulations	Uniformity of weight (n=3) Mean±SD (mg)	Thickness of patch (n=6) Mean±SD (mm)	Folding endurance (n=3) Mean±SD	Drug content (n=3) Mean±SD (%)	Mucoadhesion strength (n=3) Mean±SD (g)
F1	348.267 ± 0.642	0.362 ± 0.0054	309 ± 0.58	96.88%	13.13 ± 0.153
F2	391 ± 0.529	0.369 ± 0.0047	313 ± 0.1	97.82%	13.22 ± 0.257
F3	401.633 ± 0.702	0.373 ± 0.0039	320 ± 0.005	96.26%	17.22 ± 0.104
F4	350.233 ± 0.586	0.3713 ± 0.0027	325 ± 0.221	97.89%	15.05 ± 0.132
F5	397.533 ± 0.503	0.369 ± 0.0016	329 ± 0.132	97.82%	16.53 ± 0.058
F6	410.033 ± 0.551	0.373 ± 0.0021	331 ± 0.422	98.80%	14.07 ± 0.058
F7	360.533 ± 0.503	0.372 ± 0.0001	328 ± 0.203	97.91%	14.17 ± 0.153
F8	385.833 ±0.208	0.373 ± 0.0021	332 ± 0.421	96.88%	23.23 ± 0.252
F9	420.167 ± 0.153	0.374 ± 0.0022	329 ± 0.126	95.64%	16.1 ± 0.1