Development and Evaluation of Trans Buccal Patches based on Natural and Synthetic Polymers Loaded with Rivastigmine using Solvent Casting Technique

Prasanta Kumar Mohapatra¹*, Boddu Pavan Kumar², Pankaj Singh Patel¹, Harish Chandra Verma¹, Satyajit Sahoo³

¹Moradabad Educational Trust Group of Institutions, Faculty of Pharmacy, Moradabad - 244001, Uttar Pradesh, India.

²Lydia College of Pharmacy, Ravulapalem - 533238, Andhra Pradesh, India.

³C. U. Shah College of Pharmacy and Research, Surendranagar - 363001, Gujrat, India.

*Corresponding Author E-mail: mohapatra.kjr@gmail.com

ABSTRACT:

Mucoadhesive buccal films of rivastigmine were prepared by the solvent casting technique using HPMC K15M, sodium alginate, glycerine, and Eudragit RL100. Arranged films assessed for weight variation, thickness, % drug substance, % moisture loss, % moisture take-up, folding endurance, in-vitro medicament release, and Fourier transform Infrared spectroscopy (FTIR). The films showed a controlled release (CR) over 8 h. The preparation observed to be a worthy candidate for the development of buccal patches for therapeutic purposes. Drug-polymer compatibility considers FTIR demonstrated no contradiction between the medicament and the polymers. The optimized formulation found F7 indicated drug release 85% at the end of 8 h. Thinking about the correlation coefficient (R2) values got from the kinetic equations, the drug release from the formulations F1-F8 has discovered zero-order release mechanism. It can be concluded that oral buccal patches of rivastigmine, for treatment of Alzheimer’s and Parkinson’s disease, can be formulated. The study suggests that rivastigmine can be conveniently administered orally in the form of buccal patches, with the lesser occurrence of its side effects and improved bioavailability.

KEYWORDS: Buccal Patches, HPMC K15M, Sodium Alginate, Eudragit RL100, Solvent Casting Technique.

INTRODUCTION:

The drug delivery systems (DDSs) generally comprise tablets, suspension, cream, ointment, liquid, injectable, and aerosol. Today widely used DDSs are conventional DDSs. The methods that apply to get the therapeutic agent in the human body known as drug delivery. The delivery system’s other role is to allow the safe application of the drug. So, in the formulation, the medicament must be physically, synthetically, and microbiologically steady. By the use of suitable DDSs, the side effects of the drug and drug interactions should be minimized or avoided. The convenience of drug administration should be improved by the delivery systems¹.

Any drug delivery system (DDS) attains the release of the drug over a prolonged period known as a sustained- release drug delivery system (SRDDS), which is not time-dependent. In formulating a sustained-release (SR) dosage form hydrophobic polymer matrix commonly used. The character of the ultimate DDS is to provide an accurate site of action to maintain the therapeutic range of drug in blood plasma and to deliver the right amount of medicament at a regular time intermission. The most famous form of controlled release drug delivery system (CRDDS) is an oral CRDDS, and it is the clear advantage of the oral route of drug administration. Such methods release the drug with a steady or fluctuating release rate. A typical pattern of drug release shown by the oral CRDDS, an extended period, and the drug concentration maintained in the therapeutic window. The better control of plasma drug levels, less side effect, fewer dosage frequencies, increased efficacy, and continuous transfer, delivered by CR dosage form^2,3,4. The plasma concentration of drugs within the therapeutic window, for an extended time maintained by CRDDS, to confirm sustained therapeutic action and for that purpose, a growing interest in their growth exists in hypothetical drug concentration profiles, then single doses of immediate-release, SR, and control release drug delivery systems (CRDDSs)⁵. The active agents mainly released from a delivery system by three primary mechanisms are diffusion, swelling, and degradation followed by diffusion. When a drug or other active agent permeates through the polymer by a diffusion mechanism that creates the CR device. In the polymer matrix or on a molecular level or by passing between polymer chains on a macroscopic scale as through pores, the diffusion can occur⁶. The CRDDSs have created and developed for controlling the rate of drug delivery, targeting the delivery of a drug to tissues, and/or sustaining the duration of therapeutic activity⁷. An important route of drug administration has lately discovered is a buccal drug delivery (BDD). For BDD, several bio-adhesive mucosal dosage forms developed, like gels, ointments, adhesive tablets, patches, and more recent film. In the mid-1980's the idea of mucosal adhesive or mucoadhesive introduced into the CRDDS. The adhesive attached to mucosal is natural or synthetic polymers that intermingle with the mucus layer cover up the epithelial surface of mucosal and mucin molecules, which is organizing a major part of the mucus⁸. The likelihood that these polymers can be utilized to defeat physiological boundaries to long-term drug delivery, this idea of mucoadhesive has informed by numerous investigators⁹. The investigators made the treatment safer and more effective, not only for topical disorders but also for systemic difficulties¹⁰. An Acetylcholinesterase Inhibitor drug rivastigmine inhibits both Acetylcholinesterase and Butyrylcholinesterase (unlike Donepezil, which selectively inhibits Acetylcholinesterase). It is better to work by preventing these cholinesterase enzymes, which would otherwise collapse the brain Neurotransmitter acetylcholine¹¹. The established treatment effects of rivastigmine have on the cognitive (memory and thinking), functional (activities of daily living) and behavioral problems generally linked with Alzheimer's^12,13,14 and Parkinson's disease dementias¹⁵. Orally or via a transdermal patch the drug rivastigmine can be administered; the latter decreases the occurrence of side effects,¹⁶ which typically consist of nausea and vomiting¹⁷. The drug rivastigmine is excreted through the urine and performs to have relatively rare drug-drug interactions¹⁷. It is a white to off-white, fine crystalline powder i.e., both hydrophilic (soluble in water) lipophilic (soluble in fats) and it arises in a multiplicity of administrations, including a capsule, solution, and transdermal patches. Comparable to other Cholinesterase Inhibitors¹⁷ bio-adhesive patches are used in the mouth, which releases the drug after contact with oral mucosa and absorbs directly by entering into a systemic solution. The patches are commonly prepared by a solvent evaporation technique¹⁸. The objective of this study was to prepare rivastigmine mucoadhesive buccal patches and evaluate their properties.

MATERIALS AND METHODS:

Materials:

Rivastigmine was procured as a gift sample from Indian Immunologicals Ltd, Gachibowli, Hyderabad, India. The Eudragit RL100 and HPMC K15M Purchased from Otto Chemicals and Oxford Chemicals. Sodium alginate, plasticizer, and glycerine procured from Rankem Pvt Ltd, India. All other chemicals are of analytical grade, procured from the authorized dealer^19,20,21,22.

Drug-polymer Compatibility:

To explore any conceivable collaboration between the medication and the used polymers under scrutiny, FTIR spectrophotometer strategy utilized. In FTIR study the pure drug rivastigmine and a physical blend of pure drug and polymers accomplished on Tensor 27, Bruker Optics, Germany by a KBr dispersion method. The 400 cm^-1 to 4000 cm^-1 range selected for FTIR spectra (Fig. 3 and 4 )23,24,25,26.

Determination of λ Max of Rivastigmine in 6.8 pH Buffer:

The required quantity (100mg) of pure drug rivastigmine dissolved in 6.8 pH to make a solution of 1000µg/ml in a 100ml volumetric flask. By diluting the above solution to 10µg/ml, then the solution scanned between 200- 400nm range to get maximum absorption. From the spectra of drug rivastigmine, maximum absorption 262nm selected for the analysis^21,27.

Calibration Curve of Rivastigmine with 6.8 Phosphate Buffer:

A stock solution containing 1mg/ml of the pure drug prepared by dissolving 100mg of rivastigmine insufficient 6.8 pH buffer to produce a 100ml solution in a volumetric flask. From the 1000µg/ml standard stock solution, 1ml, 2ml, 3ml, 4ml, 5ml of solution were pipette out into 10ml volumetric flasks. The volume made up to mark with buffer. These dilutions give 100 µg/ml, 200µg/ml, 300µg/ml, 400µg/ml and 500µg/ml concentration of rivastigmine, respectively. The calibration crook fed in the concentration range of 100- 500µg/ml at 262nm. The concentration of the sample solution by using the calibration curve can be determined^21,24.

Preparation of Mucoadhesive Buccal Patches:

The Solvent casting method employed to prepare buccal patches by using HPMC K15M, Sodium alginate, and Eudragit RL100 as polymers. According to the lot formula, all the ingredients in hold pharmaceutical, polymer, and excipients estimated even.

Table 1: Composition of Different Buccal Mucoadhesive Formulations.

Compounds	F1	F2	F3	F4	F5	F6	F7	F8	F9
Rivastigmine (mg)	70	70	70	70	70	70	70	70	70
Sodium Alginate (mg)	500	*	*	750	*	*	325	325	*
Eudragit RL100 (mg)	*	500	*	*	750	*	325	*	325
HPMC K15M (mg)	*	*	500	*	*	750	*	325	325
Glycerine (ml)	65	65	65	65	65	65	65	65	65
Methanol (ml)	*	20	*	*	20	*	20	*	20
Water (ml)	Up to 30 ml	Up to 30 ml	Up to 30 ml	Up to 30 ml	Up to 30 ml	Up to 30 ml	Up to 30 ml	Up to 30 ml	Up to 30 ml

Note: * the particular excipient not utilized in the formulation

The medicament and all the ingredients have taken on a butter wallpaper with the aid of a stainless-harden spatula than the ingredients dissolved in the water containing measuring glass. After dissolving the drug and polymers completely, plasticizer and permeation enhancer added. Then the complete solution transferred to a petri plate and kept for drying and patches are collected^24,28,29.

Statistical design:

Most formulation strategy contains the variation of one factor at a time, keeping other factors steady. Such an empirical technique is satisfactory, but when factors are independent of each other. The factorial designs permit all factors to change, in this way permitting evaluation of the impact of every factor at each point and indicating interrelationship among them. A statistical model encompassing interactive and polynomial expressions utilized to evaluate the reactions. A factorial design utilized sequentially to study the outcome of independent formulation variables (amount of sodium alginate, Eudragit RL100, HPMC K15M, and Methanol) specified as factors X1, X2, X3 and X4 on the release profile of rivastigmine from mucoadhesive buccal patches. Table 2 summarizes a record of the nine-formulations examined, their factor combinations, and the coded levels of the experimental units utilized during the study^4,34.

Table 2: Experimental Factorial Design Layout.

Coded levels	Coded factors and their actual values
	X1 = Sodium alginate (mg)	X2 = Eudragit RL100 (mg)	X3 = HPMC K15M (mg)	X4 = Methanol (ml)
-2	*	*	*	20
-1	325	325	325	*
0	500	500	500	*
+1	750	750	750	*
Formulation code	Coded factors and their levels
	X1	X2	X3	X4
F1	0	*	*	*
F2	*	0	*	-2
F3	*	*	0	*
F4	+1	*	*	*
F5	*	+1	*	-2
F6	*	*	+1	*
F7	-1	-1	*	-2
F8	-1	*	-1	*
F9	*	-1	-1	-2

Note: * the particular excipient not utilized in the formulation

Fig. 1: Photograph of Prepared Mucoadhesive Buccal Patch of Rivastigmine

Evaluation of the Transdermal Patches: Physical Appearance:

Mucoadhesive buccal patches visually scrutinized for color, flexibility, homogeneity, and smoothness^19,30.

Thickness and Weight Variation:

By using a thickness gauge, the thickness of the patch at three unalike points determined. To decide the mass of individual patch, the patch separated from the cast patch and the patches weighed independently utilizing a digital balance. The weight variation performed by individually weighing ten randomly selected patches. Same as the test carried out for each formulation^24,29,31,32.

Folding Endurance:

In the laboratory by designing an apparatus, the folding endurance test for patches (2cm x 2cm) executed. For the folding endurance test, the disintegration mechanical assembly was reworked. For holding the patch, the device comprises two braces. Out of two clamps, one clamp was a constant place while another clamp was moving provision. The movable clamps moved 5cm distance at a speed of 30rpm. The patch will be slightly stretched when the patch was at a maximum distance. Until the patch broke into two pieces, the apparatus allowed to run. By rpm, the folding was counted19,24,29,33,34.

Percentage of Moisture Loss:

Accurately gauged patches of every detailing kept at room temperature in a desiccator and presented to a climate having 98% relative humidity (comprise calcium chloride anhydrous) and it weighed following three days. In tripled, the test impelled out. Difference between initial and final weight, the percentage of moisture loss was calculated^25,32,33,35.

Percentage Moisture Uptake:

In a desiccator accurately gauged patches of every formulation put at room temperature, which kept up at 79.5% relative humidity (saturated solution of aluminum chloride) and following three days gauged. In triplicate, the experiment carried out. Difference between final and initial weight, the percentage of moisture uptake was calculated^29,30,36.

Drug Content % Estimation:

Patches of the predetermined zone cut, and the pieces transferred into a 100ml volumetric flask comprising phosphate buffer (pH 6.8), and the flask sonicated for 8

h. A blank set up in a similar way utilizing a medicament-free placebo patch of similar dimensions. By utilizing a 0.45μm filter, the solution filtered and the content of the drug analyzed at 262nm by UV-Vis spectrophotometer^{9,27,34,37,38}.

In-vitro Drug Release Studies:

The in-vitro release studies impelled out by applying the diffusion mechanism in a glass beaker with the help of a modified magnetic stirrer. The compartment maintained at 37±1°C employing an electric control circulator and also verified manually by using a thermometer. The compartment loaded up with newly arranged phosphate buffer pH 6.8. The solvent in the receptor compartment persistently mixed at 60 rpm utilizing a Teflon covered magnetic stirrer, in command to shun diffusion layer expression. The commercial semi-porous layer mounted between the giver and receptor compartment and verified set up by methods for a brace. The patch set on one side of the semi-penetrable layer. Aliquots of 1 ml were remote from the receptor pigeonhole by methods for a syringe and supplanted promptly with a similar volume of support arrangement kept at 37±1°C. Test samples taken from the medium at predetermined time intervals throughout 8 h the samples analyzed for rivastigmine content by UV-Vis spectrophotometer at 262 nm^20,24,28,29.

Kinetics of Drug Release:

The diffusion kinetics of the rivastigmine analyzed by a graphical method for zero-order, first-order, Higuchi, Hixon-Crowell, and Peppa’s exponential equation. To study the study kinetics, data obtained from the in-vitro release plotted in various kinetic models^4,24,39.

Zero-order Model:

From the pharmaceutical dosage forms dissolution of the drug does not disaggregate and release the drug little by little and the graph plotted as % drug released Vs time in ‘h’ can be expressed by

Qt = Q0 + k0t                                                                             (1)

Where,

Q0 = Initial concentration of drug at time t = 0 Qt = Amount of drug dissolved at a time t

K0 = Zero-order constant in concentration/time t = Time in h

First-order Model:

This model is the necessity to decide the absorption and/or elimination of some drugs, regardless of whether it is hard to conceptualize this mechanism on a hypothetical premise. The diagram was a conspiracy as a log % cumulative drug last Vs time in ‘h’.

Log Qt = log Q0 – Kt / 2.303                                                  (2) Where,

Qt = Percent of drug remaining at time t Q0 = Initial concentration of drug

K = First-order constant t = Time in h

Higuchi Model:

It is a first mathematical model that defines drug release from a matrix system, recommended by Higuchi in 1961. The intrigue graph drowned % cumulative drug discharged Vs square root of time.

Qt = KHt^1/2                                                                               (3)

Where,

Qt = Amount of drug released at time t per unit area A KH = Higuchi dissolution constant reflecting design variable system

t = Time in h

Hixon Crowell Model:

The particles that have a uniformed size, the equation derived by Hixson and Crowell describes the dissolution rate based on the weight of the particles cube root and the particle radius not assumed to be variable.

It is calculated by the equation,

Q ^1/2 - Q ^1/2 = K t                                                                     (4)

In the pharmaceutical dosage form, the incipient amount of medicament is Q0 and the rest of the measure of medication in the pharmaceutical dosage form is Qt at a time ‘t’ and ‘KH’ is a Hixson-Crowell proportionality consistent. From the acquit kinetics, information acquired from in-vitro medicament release studies plotted as the cube root of % medicament remaining Vs time in ‘h’^24,39.

Korsmeyer Peppa’s Model:

Mt/ M∞ = K tⁿ (5)

Where the quantity of drug release at time t is Mt, and the amount released at a time is M∞ where t =∞, thus Mt

/ M∞ is the at a time ‘t’ fraction of drug released, the kinetic constant known as ‘k’, and diffusion exponent is ‘n’ and for both solvent penetration and drug release mechanism characterized by the above equation. The correlation coefficient set up by executing the obtained data into various kinetic models. From the slope, the rate constants of respective models calculated. The ‘n’ esteem utilized to portray different releases for mucoadhesive film substances and depicted in Table 5. For the occasion of film, Fickian diffusion relates when

n ≤ 0.50 and non-Fickian transport relates 0.50 < n < 0.10, Case II (relaxational) transport obey when n = 0.10, and in case of n > 0.10 obeys super case II transport^40,41,42.

RESULTS AND DISCUSSION:

Calibration Curve Preparation:

Calibration curves of rivastigmine in phosphate buffer pH 6.8 solutions constructed at λ max 262nm with a (Shimadzu Corporation, Kyoto, Japan). Beer’s law obeyed to construct the calibration curve was in the concentration range of 100-500μg/ml. The analysis done in triplicate²⁴.

Table 3: Calibration Curve of Rivastigmine in 6.8 pH Buffer.

Concentration (µg/ml)	Absorbance (Mean ±SD)
0	0
100	0.133
200	0.272
300	0.41
400	0.545
500	0.678

Fig. 2: Calibration Curve of Rivastigmine in 6.8 pH Buffer

Physical Appearance:

All the mucoadhesive buccal patches formulated utilizing different concentrations of polymer were achieved transparent, uniform, smooth, flexible, and homogeneous^19,30,43.

Thickness Uniformity:

All the patches have found uniform thickness. The mucoadhesive buccal film thickness was found between 0.225±1.1 mm to 0.268±1.1 mm^24,35,43.

Percentage of Moisture Loss:

Precisely weighed patches of all formulation held at room temperature in a desiccator and introduced in an environment of 98% relative dampness (comprising anhydrous calcium chloride) and weighed the following three days. The test moved out in treble. The moisture loss percentage determined by calculating the difference between the initial and final weight concerning initial weight at the dry condition. The achieved values were between 5.10±0.3% to 12.42±0.4%^32,35.

Percentage Moisture Uptake:

Correctly gauged patches of each formulation placed in a desiccator and which was 79.5% relative moisture, previously mentioned (comprise aluminum chloride saturated solution) at room temperature and following three days similar patches gauged. The test performed in triplicate. When the formulations contain standard moisture content, the film remains stable, non-brittle, and free from complete drying. The optimum standard of moisture absorption found in formulation F1, F4 and F7, so there is less chance of microbial contamination and maintaining integrity in the entire shelf life. The percentage of moisture uptake calculated by initial and final weight and the founded range was 4.64±0.03% to 10.33±0.01% (Table 4)^29,35,44.

Folding Endurance:

An idea about the flexibility or brittleness of films specified by folding endurance. Good limberness gives high excellence of folding endurance, but fragility films give a less value of folding endurance. All the films didn’t show any crack or cut after over 200 times, folding according to the obtained results, and all were having acceptable flexibility. The results observed in Table 429,35,37.

Weight Variation Test:

All the film's weight found to be uniform. The weight found between 99.09±1.1 mg to 100±1.2 mg. It observed from the obtained results that by increasing the polymer concentration the weight of the film also increases. Any deviation in the film's weight leads to under-dosage or overmedication possessed by a momentary feature known as weight variation test. The weight results shown in Table 4^24,26,35.

Drug Content Percentage:

The accurate distribution of the drug ensured by the drug content estimation. For every formulation, the test is done in triplicate, and arise results were ready in Table 4. The results indicate that the drug uniformly dispersed means proper content, uniformity found. The percentage of drug content found between 92.41±0.1% to 98.59±0.6%^24,31,38.

Drug-polymer Compatibility:

FTIR spectra of pure drug and a mixture of the pure drug and polymers introduced in Fig. 3 and 4. FTIR spectrum of pure drug rivastigmine displays the peaks at 666.79 cm^-1, 902 cm^-1, 1125 cm^-1, 1228.33 cm^-1, 1401.33 cm^-1,

and 1691.39 cm^-1. These peaks can be reflected as characteristic peaks of rivastigmine not affected and detected in the FTIR spectra of rivastigmine together with polymers as presented in Fig. 4, which showed that between drug and polymers there was no interaction²⁴.

Table 4: Physicochemical Evaluation Data of Rivastigmine Patches.

Formulation Code	Appearance	Surface Texture	% Moisture Loss*	% Moisture Uptake*	Folding Endurance	Thickness (mm)*	Weight Variation (mg)*	% Drug Content*
F1	+	VS	9.36 ± 0.6	4.64 ± 0.05	>200	0.248 ± 0.6	99.87 ± 1.4	94.9 ± 1.3
F2	+	VS	8.63 ± 0.4	7.25 ± 0.07	>200	0.225 ± 1.1	99.7 ± 1.9	96.5 ± 0.8
F3	+	VS	5.75 ± 0.6	6.04 ± 0.04	>200	0.234 ± 0.8	99.09 ± 1.1	94.5 ± 0.9
F4	+	VS	9.36 ± 0.7	4.64 ± 0.06	>200	0.268 ± 1.1	99.87 ± 1.4	96.5 ± 0.8
F5	+	VS	8.63 ± 0.8	7.25 ± 0.09	>200	0.256 ± 0.9	99.98 ± 1.2	94.9 ± 0.8
F6	+	VS	8.96 ± 0.6	6.04 ± 0.05	>200	0.258 ± 0.7	99.5 ± 1.8	94.28 ± 1.5
F7	+	VS	12.42 ± 0.4	4.64 ± 0.03	>200	0.248 ± 0.6	99.7 ± 1.9	93.45 ± 0.8
F8	+	VS	5.10 ± 0.3	10.33 ± 0.01	>200	0.225 ± 1.1	99.09 ± 1.1	98.59 ± 1.6
F9	+	VS	8.76 ± 0.2	8.18 ± 0.04	>200	0.234 ± 0.7	100 ± 1.2	92.41 ± 0.9

*Each Value Represents the Mean ±S.D. (n=3) (VS = Very Smooth)

In-vitro Drug Release:

The release data of rivastigmine from all the patches given in Fig. 5, 6 and 7. It indicates that the drug release time was highest in combinations of sodium alginate and Eudragit RL100 in F7. At pH 6.8, when contrasted to F1

and F3, the formulation F2, the release rate of the drug is slow, might be because of the existence of Eudragit RL100. The data of the in-vitro release fit into different equations and kinetic models to explain the release kinetics of rivastigmine from these buccal patches.

Fig. 3: FTIR Sample for Rivastigmine (Pure Drug)

Fig. 4: FTIR Sample for Optimized Formulation

The release kinetics of rivastigmine followed a zero- order from the patches F1 to F8. The release rate of the drug in polymers was in this pattern Eudragit RL100 < sodium alginate < HPMC K15M. From this data, it found that the release rate found slower by using

Eudragit RL100 than others. Again, the formulations F7, F8 and F9 made by combining of two polymers and compared with formulations having more amount of polymer and it found that a combination of polymers gives a good result means extended-release, hence the

mechanism of drug release from the rivastigmine patches followed is dissolution controlled. In the formulations F1 to F9, glycerin used as a permeation enhancer. When compared to all the formulations it indicated by the rivastigmine patches in Fig. 5, F7 released 85% of the drug in 8 h^24,28,35.

Fig. 5: In-vitro Drug Release Profile of F1, F4, F7 Rivastigmine Buccal Patches

Fig. 6: In-vitro Drug Release Profile of F2, F5, F8 Rivastigmine Buccal Patches

Fig. 7: In-vitro Drug Release Profile of F3, F6, F9 Rivastigmine Buccal Patches

Kinetics of Drug Release:

The drug release data then fitted to mathematical models such as a zero-order, first-order, Higuchi, Hixon-Crowell and Korsmeyer-Peppas model and the coefficients of regression values compared. The regression value of films F1 to F8 follows zero-order and only F9 follows Higuchi release, therefore, the release kinetics followed

by zero-order. According to the Korsmeyer-Peppas model, the value of slope ‘n’ is between 0.94 to 1.71 so it indicates the diffusion behavior. The formulation F1 indicate that the release mechanism from the films follows non-Fickian diffusion n=0.94 (0.50 > n > 0.10) and formulations F3, F7, F9 release mechanism from the films follows Case II (relaxational) transport obey when n = 0.10, The remaining formulations F2, F4, F5, F6 and F8 follows super case II transport (n > 0.10) Table 522,27,36.

Table 5: In-vitro Drug Release Kinetic Studies of Different Rivastigmine Buccal Patches.

Formulation Code	Zero- order	First- order	Higuchi	Hixon Crowell	Release Exponent (n)
	(R^2)
F1	0.959	0.903	0.806	0.927	0.94
F2	0.984	0.912	0.948	0.946	1.324
F3	0.996	0.934	0.994	0.971	1.008
F4	0.987	0.849	0.963	0.919	1.133
F5	0.985	0.884	0.959	0.933	1.321
F6	0.97	0.899	0.935	0.938	1.71
F7	0.946	0.814	0.929	0.876	1.096
F8	0.974	0.832	0.924	0.895	1.258
F9	0.979	0.969	0.992	0.984	1.088

(R² = Regression Coefficient), (n = Release Exponent).

CONCLUSIONS:

By using rivastigmine as a model drug, buccal films prepared using various polymers by the method of solvent casting technique. In the present study, nine formulations prepared using three polymers in different ratios, along with plasticizers and penetration enhancers. Finally, it concluded that the highest drug release obtained with the film containing sodium alginate and Eudragit RL100 in combination in formulation F7 which showed a drug release of 85% at the end of 8 hours. From the result of in-vitro drug permeation studies, it found that the release kinetics follow zero-order drug release except for F9. Accordingly, rivastigmine can be helpfully managed orally as buccal films with the lesser event of its side effects and enhanced bioavailability.

ACKNOWLEDGEMENT:

The authors are grateful to Indian Immunological Ltd, Gachibowli, Hyderabad, India for providing drug rivastigmine as a gift sample.

CONFLICT OF INTEREST:

The authors have declared no conflict of interest.

AUTHORS CONTRIBUTIONS:

All the authors have contributed equally

STATEMENT OF HUMAN AND ANIMAL RIGHTS:

With human or animal subjects, this clause does not hold any studies or performed by any of the authors.

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Received on 20.04.2020              Modified on 12.10.2020

Accepted on 19.01.2021             © RJPT All right reserved

Research J. Pharm. and Tech. 2021; 14(10):5133-5140.

DOI: 10.52711/0974-360X.2021.00894