Journal of Pharmaceutical Investigation (2013) 43:133–143 DOI 10.1007/s40005-013-0062-7
RESEARCH ARTICLE
Mathematical optimization and characterisation of pharmaceutically developed novel buccoadhesive wafers for rapid bioactive delivery of Loratadine Prithviraj Chakraborty • Versha Parcha • Debarupa D. Chakraborty • Indranil Chanda Amitava Ghosh
•
Received: 26 January 2013 / Accepted: 26 February 2013 / Published online: 16 March 2013 Ó The Korean Society of Pharmaceutical Sciences and Technology 2013
Abstract The purpose of this study was to develop pharmaceutically active buccoadhesive wafer formulations containing Loratadine and mathematically optimize the influence of bioadhesive polymer Sod. CMC and Lactose monohydrate as an ingredient of wafer base matrix, on the physicochemical and drug release performance from the prepared wafers. The wafers, which were prepared by the solvent casting method, were smooth and elegant in appearance; uniform in thickness, weight and drug content; showed no visible cracks; and demonstrated good folding endurance. A 32 factorial design was employed to study the effect of independent variables like Sod.CMC and Lactose monohydrate, which significantly influenced characteristics like buccoadhesion, swelling index, disintegration time and t70 % of the prepared wafers. The drug-excipients interaction studies performed by ATR-FTIR, DSC and XRD revealed drug polymer compatibility within the wafer formulation. Surface morphology of the prepared wafers were studied by using SEM. Drug release study in the buccal environment showed the efficacy of the wafers to release drug within a very short span of time. Thus a conclusion
P. Chakraborty (&) D. D. Chakraborty A. Ghosh Bengal College of Pharmaceutical Sciences and Research, Durgapur, West Bengal, India e-mail:
[email protected] V. Parcha Department of Chemistry, Sardar Bhagwan Singh PG Institute of Biomedical Sciences and Research, Balawala, Dehradun, Uttarakhand, India I. Chanda Girijananda Chowdhury Institute of Pharmaceutical Science, Azara, Hatkhowapara, NH-37, Guwahati, India
might be brought forward that the present buccal wafer formulation could be an ideal system improving the bioavailability of the drug by avoiding hepatic first pass metabolism and would be an ideal alternative for the patients suffering with dysphagia. Keywords Wafer Mathemetical optimization Buccoadhesive RSM Loratadine
Introduction Drug delivery targeting specialized area of population is now a day’s boom like anything. A tremendous emphasis is given to develop a suitable dosage form which will give better patience compliance. Fast-dissolving films attend to the need of population requiring special attention, such as paediatric and geriatric patients with difficulty in swallowing medicine. This often leads to non-compliance with medication for this group of population causing ineffective treatment. As the oral cavity is an attractive site for drug delivery, Oro-dissolving films could be the way of choice to overcome these difficulties with additional advantages like increase of drug absorption, addition of patent life of existing drugs, eradication of the need for water, and improve ease of taking medicines while itinerant and for patients with limited water intake (Saigal et al. 2008). Literature reports different synonyms like wafer, oral film, thin strip, orally dissolving film, and flash release wafer, quick dissolve film and melt-away film for these types of delivery systems (Hoffmann et al. 2011). Buccal drug delivery specifically refers to the delivery of drugs within/through the buccal mucosa to affect local/ systemic pharmacological actions. Buccal-delivered drugs
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may be used for treatment of diseases in the oral cavity or for systemic use (Hao and Heng 2003). Buccal mucosa contains admirable accessibility because of a high region of smooth muscle and relatively static mucosa which allows administration of retentive dosage forms. High bioavailability is observed due to direct access of drug to the systemic circulation through the internal jugular vein, bypassing the hepatic first pass metabolism. Other advantages includes low enzymatic activity, appropriateness for drugs or excipients that may damage or irritate the mucosa, unproblematic administration, ease of drug withdrawal, facility to incorporate permeation enhancers/enzyme inhibitors or pH modifiers in the formulation and robustness in designing as multidirectional or unidirectional release systems for local or systemic actions (Sudhakar et al. 2006). Film releasing drug towards the buccal mucosa targets absorption of drug through the venous system that drains from the cheek to avoid the first pass effect (Morales and McConville 2011). Loratadine (LOR), a tricyclic, piperidine derivative of antihistamines, is a non-sedative second generation H1 receptor blocker which is under class II of the Biopharmaceutical Classification System. It is available commercially as mono component tablet (Claritin) (Abu-Lathou et al. 2005). It is an ionisable drug, whose solubility depends on the gastrointestinal pH, and the bioavailability is therefore very variable (Szabados-Nacsa et al. 2011). Use of LOR by aircrew is also approved by various civil and military authorities for mild or moderate allergic symptoms or other situations necessitates an antihistaminic (e.g. urticaria) due to its non sedative effect which is a common side effect shown by older first-generation antihistamines, such as diphenhydramine and chlorpheniramine to produce sedation (Onozawa et al. 2008). Literature also suggested LOR may exert an in vivo antiinflammatory effect (Gelfand et al. 2004). The major investigation of the present study includes development of a buccoadhesive pharmaceutical wafer formulation containing LOR with a bioadhesive polymer, sodium carboxy methyl cellulose (Sod. CMC) and lactose monohydrate (LACTOSE) as a hydrophilic base forming material and to mathematically optimize the influence of these two factors on the physicochemical properties and drug release of the developed buccoadhesive wafer formulations.
P. Chakraborty et al.
400 were obtained from Merck Specialities Pvt. Ltd., India; sorbitol (liquid 70 %) was procured from CDH, India; glycerol was purchased from Loba chemie, Mumbai, India. All the other chemicals and solvents used were of AR grade and used without further purification. Methods Experimental design The wafers were prepared according to the 32 factorial design, where the amount of the two carrier(s) (factors) was varied at three levels as postulated by the design. The amount of Sod. CMC as a bioadhesive polymer (X) and lactose monohydrate as a matrix former (Y) were studied at three levels according the experimental design as shown in Table 1. The dependent variables studied were bioadhesive force (Y1), % Swelling Index (Y2), Disintegration time (Y3) and time taken for the release of 70 % of drug (t70% or Y4). Preparation of LOR bioadhesive pharmaceutical wafers
Materials and methods
Numerous literatures had revealed the use of solvent casting method to prepare bioadhesive thin films or wafers (Cilurzo et al. 2008; El-Setouhy and El-Malak 2010). Here we have utilized this procedure for development of the wafers. 2 % w/v of HPC was considered as film forming polymer and mixed with varied amount of Sod. CMC as per the experimental design (Table 2), where HPC concentration was kept constant in all formulations and was dispersed in required volume of distilled water and kept overnight for soaking. A constant proportion of propylene glycol, glycerine and sorbitol were used as plasticizers. Required amount of LOR dissolved in aliquot of ethanol was dispersed in the polymer dispersion with continuous stirring. Lactose monohydrate was added in the dispersion with continuous stirring followed by addition of saccharine sodium (sweetner) and peppermint (flavour). The stirring process of the total polymeric dispersion was continued for 6 h. The dispersion was kept in degasser for 180 s to remove any dissolved gas. 25 ml of the solution was casted in polypropylene petri plates (Polylab Industries Pvt. Ltd., India) and kept overnight to remove the entrapped air bubbles. The content of the plates were dried at 45 °C. Wafers of 2.2 diameters were cut with in-house fabricated hollow punch and kept in desiccator, maintained at a relative humidity of 60 ± 5 % until further analysis.
Materials
Evaluation of buccoadhesive pharmaceutical wafers
LOR, hydroxy propyl cellulose (HPC) (Klucel) and saccharine sodium were purchased from Yarrow Chemical Products, Mumbai, India; sodium carboxy methyl cellulose (Sod. CMC), lactose monohydrate, polyethylene glycol
Thickness uniformity analysis
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The thickness of each wafer was measured using a micrometer (Mitutoyo, Tokyo, Japan) at five locations
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Table 1 Experimental design: factors and responses Factors (independent variables)
Level used
Responses (dependent variables)
-1
0
?1
X = Concentration of bioadhesive polymer (% w/v)
0.5
1
1.5
Y = Concentration of lactose monohydrate as hydrophilic matrix former (% w/v)
0
Table 2 Composition of experimental formulation (runs)
Y1 = Bioadhesive strength Y2 = Disintegration time
Formulation code (runs)
0.5
1
Y3 = % Swelling Index Y4 = Time taken for 70 % drug release (t70%)
Sodium CMC (X)
Lactose monohydrate (Y)
Bioadhesive strength (g)
Disintegration time (min)
% Swelling t70% (s) Index
FNC1
0
-1
24.26000
1.233000
63.860000
30.00
FNC2
0
0
32.90000
1.317000
67.190000
120.00
FNC3
0
?1
35.90000
1.487000
67.840000
150.00
FNC4
?1
-1
38.12000
1.697000
70.930000
180.00
FNC5
?1
0
44.80000
2.153000
72.550000
210.00
FNC6
?1
?1
81.20000
2.303000
72.600000
150.00
FNC7
-1
-1
52.70000
0.500000
59.890000
30.00
FNC8
-1
0
42.80000
0.873300
58.740000
90.00
FNC9
-1
?1
33.60000
1.193000
60.520000
150.00
(centre and four corners) and the mean thickness was calculated. Samples with air bubble, nicks or tears were excluded from analysis. Surface pH measurement The wafers were left to swell for 10 min on the surface of an agar plate (2 % m/v in isotonic phosphate buffer pH 6.75).The surface pH was measured by means of a pH paper placed on the surface of the swollen wafer. The mean of three readings was recorded (Nafee et al. 2003a, b). Disintegration study Disintegration study was performed following the method reported elsewhere (El-Setouhy and El-Malak 2010). The wafer size (3.80 cm2) was placed on a glass petri dish containing 10 ml of distilled water. The time required for wafer to break was noted as in vitro disintegration time. Three replicates were done for each formulation.
done at 1 h. Three wafers were tested for each formulation (Nafee et al. 2003a, b). Radial swelling was calculated from the following equation: SD ð%Þ ¼ ðDt Do Þ=Do 100 where SD (%) is the percent swelling obtained by the diameter method, Dt is the diameter of the swollen wafer after time t, Do is the original wafer diameter at time zero. Surface morphology analysis Dried placebo and drug-loaded wafers were examined under a SEM (JEOL-JSM-6360, JEOL Datum Ltd., Tokyo, Japan). SEM photographs of samples were taken at 12 kV intensity at magnifications of 250–2,000. Drug polymer Interaction analysis:
Swelling Index study
ATR–FTIR spectroscopy of prepared wafers ATR–FTIR spectra of blank wafer, LOR and LOR loaded wafer were recorded on a Bruker—ALPHA FTIR spectrophotometer with software Opus 6.
After determination of the original wafer diameter (3.80 cm2), the sample was allowed to swell on the surface of an agar plate kept in an incubator maintained at 37 °C. Measurement of the diameter of the swollen wafer was
Differential scanning calorimetry Thermal properties of placebo wafer, LOR and drug-loaded wafer were characterized using thermal analyser (Perkin–Elmer—USA, Model—JADE DSC). The experiment was conducted in an
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environment of nitrogen at the rate of 20 ml/min as purge gas and at a varied temperature range of 26–250 °C at heating rate of 10 °C/min. XRD analysis Powder XRD pattern of LOR, blank wafer and drug loaded wafer were measured using on diffractometric system (RIGAKU MAKE ULTIMA-III, JAPAN) at 1.5 mA and 30 kV over the range 2h = 5° to 50° at rate of 2h = 5°/min for obtaining further information about the state of drug in the wafers. In vitro analysis of buccoadhesion A TAXT2i Texture Analyzer was used for in vitro bioadhesion analysis of the pharmaceutical wafers taking bovine buccal mucosa as a model membrane. The buccal mucosal tissue was obtained from local slaughter house, cleaned, washed and stored at -20 °C. Preserved, cleaned and thawed buccal mucosa was hydrated with simulated saliva solution and allowed to reach normal temperature before conducting the experiment. The buccal mucosa was tied to the lower probe of the assembly. The wafer was attached to the upper probe of the assembly using double-sided adhesive. The upper probe was allowed to fall on the lower probe with test speed 0.5 mm/s and post test speed 1 mm/s. The wafer was allowed to adhere to the bovine buccal mucosa membrane with applied force 150 g, return distance 10 mm. The experiment was carried out at room temperature (Ahmad et al. 2008; Hassan et al. 2010). Dissolution experiment The in vitro drug release of the wafers has been carried out by performing the dissolution experiment in a paddle type dissolution apparatus (Excel enterprises, Kolkata, India) equipped with six baskets. In order to mimic the in vivo adhesion and to prevent the wafers from floating, each wafer was fixed to a rectangular glass slab and placed at the bottom of the dissolution vessel prior to starting the dissolution test. The dissolution medium comprised of 250 ml of simulated salivary fluid (Koland et al. 2011) pH 6.75. The rotation speed was kept at 50 rpm at 37 ± 0.5 °C. At regular intervals of time (30 s) (Garsuch and Breitkreutz 2009), sample aliquots were withdrawn, filtered through a 0.45 lm membrane filter and analyzed by UV spectrophotometer (Thermo Scientific UV1) at a fixed kmax value of 248 nm. The withdrawn amount of dissolution medium was calculated. Cumulative percentage of drug released in the respective dissolution medium was plotted as a function of time. Each formulation was tested and analyzed in triplicate (El-Setouhy and El-Malak 2010; El-Meshad and El-Hagrasy 2011).
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Statistical analysis of data The effect of independent variables on responses were observed using STATISTICA 7 (Stat Soft, Inc, Tulsa, OK). The modelling was done following second order polynomial equation including interaction and polynomial terms(Akhgari et al.2005) as Y ¼ b0 þ b1 A þ b2 B þ b3 AB þ b4 A2 þ b5 B2 þ b6 A2 B þ b7 AB2 þ b8 A2 B2 ð1Þ Statistical validity of the polynomials was established on the basis of ANOVA provided in the same software. Level of significance was measured at p \ 0 0.05. Response surface plots and contour plots resulting from equations were obtained from the above software.
Result and discussion Physical characterization of wafers Figure 1 demonstrates the thickness of the prepared wafers. The thicknesses of the prepared pharmaceutical wafers were within 0.209 mm to 0.438 mm. This range of thickness of the wafers is acceptable to the patient to be kept inside their buccal cavity without inconvenience. Inspite of Sod. CMC, containing carboxyl groups, the measured surface pH of the wafers were found to be within the range of 6.8–6.98 (Table 3). As Bottenberg et al. (1991), had reported that a low surface pH might cause damage to contacting mucosal surface, it was therefore important to determine the pH of the wafers as it will be administered in the buccal cavity (Munasur et al. 2006). The measured pH of the wafers will not cause any irritation at the site of administration i.e. buccal cavity as the pH of
Fig. 1 Thickness of the wafers
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Table 3 pH of the Loratadine wafers FNC 1
FNC2
FNC3
FNC 4
FNC 5
FNC 6
FNC7
FNC8
FNC9
6.9 ± 0.02
6.9 ± 0.011
6.96 ± 0.01
6.83 ± 0.012
6.8 ± 0.012
6.85 ± 0.011
6.89 ± 0.1
6.9 ± 0.01
6.9 ± 0.1
the wafers were almost similar to the pH of the salivary fluids i.e. 5.8–7.1 for saliva in mouth (de Vries et al. 1991). Surface morphology analysis The surface morphology studies revealed the nature and surface texture of the prepared wafers. The SEM photographs (Fig. 2a) revealed the fact that a good polymeric film base was prepared within the wafer matrix by the polymeric blend within the casting solution. Dispersed lactose along with the dispersed drug embedded in the wafer matrix is clearly evidenced in the Fig. 2b–d. ATR–FTIR interpretation The ATR–FTIR spectra (Fig. 3) of pure LOR sample shows sharp peaks at 1,700.66, 996.17, 1,433.63 and 1,220.46 cm-1. An absorption around 1,700 cm-1 was attributed to amide group due to C=O str. and N–H def. Absorption at 996 cm-1 was attributed to aryl halide group due to C–Cl str. Absorption at 1,433 cm-1 was assigned to nitro compound due to N=O str. Absorption at 1,220 cm-1 was observed due to saturated aliphatic and side chain aromatic groups present in the structure of LOR (Kemp 2009). All the principal peaks of LOR were present in drug loaded wafers (FNC) with minor differences in frequencies which confirms that there was no interaction between drug and polymers and reflects the stability of LOR in the prepared wafers.
XRD pattern of LOR showed the important crystallographic reflection at different scattering angle ranges from 3° to 50° to the inter-planner distances at 2h. However these signal intensities were very weak in the blank formulation as well as in the drug loaded wafer formulation, which indicates that most of the drug had dispersed at a molecular level in the polymeric matrices with no indication of crystalline nature of the drug in the matrices. In vitro bioadhesion study In vitro buccoadhesion test reveals that the prepared pharmaceutical wafers are having a good bioadhesion property (Table 2) which depends upon the incorporation of bioadhesive polymer into the wafers. In vitro dissolution study The in vitro drug release profile of LOR was shown in Fig. 6. As expected increase in Sod. CMC content in the wafer matrix showed decrease in LOR release from the wafers. This may be due to increase in the mechanical strength of these formulations which determines their rate of hydration and ultimate dissolution (Boateng et al. 2009). This finally affects the rate at which the drug diffused through the gel and released into the dissolution medium, but this phase lasts only for a short period of time. More than 70 % of drug release was observed within 4 min from all the prepared wafer formulations.
DSC interpretation Optimization data analysis DSC thermograms of LOR, drug loaded wafer and blank wafer were displayed in Fig. 4. LOR exhibits a sharp endothermic peak at 139.31 °C with peak height 36.3904 mW and area 1,221.117 mJ where as a blunt endothermic peak 124.99 °C was observed in the DSC thermograms of blank wafer formulation. In the DSC thermograms of prepared wafer formulation the endothermic peak of drug was retained with an additional endothermic peak at 138.09 which may be corresponding to dehydration of lactose monohydrate (Aboelwafa and Basalious 2010). XRD interpretation XRD patterns recorded for pure drug, blank wafer formulation and drug-loaded wafers were presented in Fig. 5.
In order to determine the levels of the factors which will yield an optimized wafer formulation in respect of bioadhesion, disintegration time, % swelling and time required for 70 % drug release (t70%), mathematical relationship were generated between the dependent and independent variables using statistical software STATISTICA 7 (Stat Soft, Inc, Tulsa, OK).The equation of each dependable variable are given below: Bioadhesive strength ¼ 123:43 183:77 X þ 84:59 X2 146:61 Y þ 97:47 Y2 þ 334:93 X*Y 275:55 X*Y2 165:39 X2 Y þ 166:79 X2 Y2
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Fig. 2 SEM photograph of prepared Loratadine wafers
Fig. 3 ATR–FTIR spectra of prepared wafers
Disintegration time ¼ 0:50 þ 2:27 X 0:53 X2 þ 3:37 Y 1:44 Y2 6:99 X*Y þ 3:74 X*Y2 þ 3:70 X2 Y 2:12 X2 Y2
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% Swelling Index ¼ 59:01 1:35 X þ 6:19 X2 38:89 Y þ 30:51 Y2 þ 86:43 X*Y 62:75 X*Y2 38:19X2 Y þ 26:87 X2 Y2
Bioactive delivery of Loratadine
139
Fig. 4 DSC thermograms of pure drug (LOR API), blank wafer (FNC BLANK) and drug loaded wafer (FNC)
Fig. 5 X-Ray diffraction pattern of pure drug, blank wafer and drug loaded wafer (FNC)
Drug Release profile of wafers composed as per formulation code FNC
150
FNC 1 FNC 2
Cum. % drug release
Fig. 6 Release profile of drug from different wafer compositions prepared in accordance with the experimental design
FNC 3
100
FNC 4 FNC 5 FNC 6
50 FNC 7 FNC 8 FNC 9
0 0
100
200
300
Time in seconds
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Table 4 Analysis of variance (ANOVA) of dependent variables SS
df
MS
F
p
ANOVA for bioadhesive strength; R2 = 0.94544; Adj: 0.85451; MS residual = 39.50779 (1) Sodium CMC L ? Q
841.645
2
420.8225
10.65163
0.043370
(2) LACTOSE L ? Q
245.578
2
122.7889
3.10797
0.185726
1*2
966.588
1
966.5881
24.46576
0.015855
Error
118.523
3
39.5078
2172.334
8
Total SS
ANOVA for disintegration time; R2 = 0.97527; Adj: 0.93405; MS residual = 0.0217663 (1) Sodium CMC L ? Q
2.167203
2
1.083602
49.78349
0.005002
(2) LACTOSE L ? Q
0.406127
2
0.203063
9.32926
0.051551
1*2
0.001892
1
0.001892
0.08693
0.787337
Error Total SS
0.065299 2.640521
3 8
0.021766
ANOVA for Swelling Index; R2 = 0.97664; Adj: 0.93771; MS residual = 1.870511 (1)Sodium CMC L ? Q (2)LACTOSE L ? Q
227.6654
2
113.8327
60.85647
0.003731
6.6699
2
3.3349
1.78290
0.308852
1*2
0.2704
1
0.2704
0.14456
0.729112
Error
5.6115
3
1.8705
240.2172
8
Total SS
ANOVA; for t70%; R2 = 0.91799; Adj: 0.78132; MS residual = 858.3333 (1) Sodium CMC L ? Q
14,600.00
2
7,300.000
8.504854
0.058052
8,600.00
2
4,300.000
5.009709
0.110610
1*2
5,625.00
1
5,625.000
6.553398
0.083217
Error
2,575.00
3
858.333
31,400.00
8
(2) LACTOSE L ? Q
Total SS
SS sum of square, df degree of freedom, MS mean square
t70% ¼ 179:99 449:99 X þ 299:99 X2 209:99 Y þ 179:99 Y2 þ 869:99 X*Y 419:99 X*Y2 419:99 X2 Y þ 119:99 X2 Y2 As reported by Dhiman et al. 2008, the first integer value represents the intercept value of the arithmetic average for each response, of quantitative outcomes of all nine runs. The terms XY were representative of the interactions. The main effects (X and Y) correspond to the average result of changing one factor at a time from its low to high value. The interaction terms (XY) shows tendency of response when two factors are changed concurrently. The polynomial terms are integrated to explore nonlinearity. The polynomial equation was used to draw a prediction after considering the magnitude of coefficients and their mathematical signs i.e. a positive sign signifies synergistic effect, whereas a negative sign indicates an antagonistic effect. Statistical testing of the model was done by the Fisher’s statistical test for analysis of variance (ANOVA) and the results are shown in Table 4. The analysis of variance of the linear and quadratic regression models and a higher F value of the models dictate that the models are highly significant. The closer the
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values of R2 to 1, the better the correlation between the observed and predicted values. Here the values of R2 = 0.94544, 0.97527, 0.97664 and 0.91799 for responses Y1, Y2, Y3 and Y4 indicates an excellent correlation between the experimental and predicted values. The p values are used as a tool to check the significance of each of the coefficients, which, in turn, are necessary to understand the pattern of the mutual interactions between the best variables. The smaller the magnitude of p, the more significant is the corresponding coefficient (Kunamneni et al. 2005). The parameter estimates and the corresponding p values (Table 4) suggest that among the independent variables Sod. CMC (X) and lactose monohydrate (Y) have a significant effect on the dependent variables (responses). The quadratic term of these two variables also have a significant effect. The response surface plots for all the responses as a function of Sod. CMC versus lactose monohydrate are shown in Fig. 7. A steeper ascent in the surface response plot for bioadhesive strength (Y1) was found for Sod. CMC (Fig. 7a) which ensures the predominance of Sod. CMC over lactose monohydrate to be responsible for increase in the bio
Bioactive delivery of Loratadine
Fig. 7 a Response surface plots showing the influence of sodium CMC and lactose monohydrate on the response Y1. b Response surface plots showing the influence of sodium CMC and lactose monohydrate on the response Y2. c Response surface plots showing
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the influence of sodium CMC and lactose monohydrate on the response Y3. d Response surface plots showing the influence of sodium CMC and lactose monohydrate on the response Y4
Fig. 8 Correlation of testing RSM model
adhesiveness of the prepared wafers. The effect of lactose monohydrate is much higher than Sod. CMC for the response Y2 i.e. for the disintegration time of the wafers (Fig. 7b) whereas, effect of Sod. CMC is leading over
lactose monohydrate for the response Y3 (% Swelling Index) and Y4 (t70%) which is visualized in Fig. 7c, d. In order to check approximation between the fitted model and actual experimental observations, plots of
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residuals versus the predicted values was investigated in Fig. 8. The distribution of scattered points in Fig 8 reflected accuracy of the predicted response explaining the observed response. It reflected that the RSM prediction approached is very high, resulted the RSM model fitted the experimental data with an admirable accuracy (Wang et al. 2010).
Conclusion In this experiment, quick disintegrating pharmaceutical wafers were formulated containing LOR, using solvent evaporation technique in a highly aqueous environment, by using an experimental design which allowed the rapid screening of a large experimental domain in search of the best concentration of ingredients to prepare of a hydrophillic wafer matrix for quick delivery of drug through buccal cavity. The wafers were characterized by SEM, ATR– FTIR, DSC and XRD technique. The bioadhesion study revealed the appropriate buccoadhesion property of the prepared wafers to be retained within the buccal cavity. The in vitro drug release study showed 70 % of drug released within 4 min from the wafers at simulated salivary pH. The results of the study indicate that drug loaded wafers could be used to minimize the problem associated with the patients with dysphagia or aphagia that require an immediate release of medicament to relief from the allergic conditions without any invasive procedure or the possible degradation of drug through first pass metabolism . Acknowledgments The authors are thankful to Department of Pharmaceutical Sciences; Dibrugarh University, Assam, India, for providing DSC facility, Department of Metallurgy, Jadavpur University, Kolkata, India for providing SEM and XRD facilities and Prof. (Dr.) S.K Dash and Mr. Pulak Deb, Girijananda Institute of Pharmaceutical Sciences, Guwahati, Assam, India, for providing TAXT2i Texture Analyzer facility.
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