Sharma et al Journal of Drug Delivery & Therapeutics.

2019; 9(4):57-64

Available online on 15.07.2019 at http://jddtonline.info

Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research
© 2011-18, publisher and licensee JDDT, This is an Open Access article which permits unrestricted
non-commercial use, provided the original work is properly cited

Open Access Research Article

Enhancing the Solubility and Dissolution Rate of Meclizine Hydrochloride by
Inclusion Complex
Sanjay Kumar Sharma*, Dr Rakesh P Patel
1Research scholar, Department of Pharmaceutical Sciences, Pacific University, Udaipur (Rajasthan)-201301, India

ABSTRACT
Meclizine Hydrochloride is an Anti-Histamine drugs with very low bioavailability that can be improved by increasing its solubility and
dissolution rate. The aim of this study is to enhance dissolution of Meclizine Hydrochloride as a model hydrophobic drug through application of
inclusion complex technology. It was formulated as inclusion complex compact, and its dissolution property is evaluated and c ompared with
marketed product of Meclizine Hcl tablet. The newly formulated drug and the interaction between excipients was examined by, Fourier-
transform infrared spectroscopy, and differential scanning colorimetry, respectively. Both DSC and SEM results suggested loss of crystallinity of
Meclizine Hydrochloride upon conversion into a inclusion complex formulation. The dissolution efficiency of Meclizine Hydrochloride at 45 min
was increased from directly compressed tablet to 98.0% for marketed product to 97.2% at 45 minutes for the inclusion complex formulation.
The increase in the dissolution rate was also found to be significant compared to the marketed product. The inclusion complex technique
appears to be a promising approach for improving the dissolution of poorly soluble drugs like Meclizine Hydrochloride.
Keywords: Meclizine Hydrochloride, inclusion complex, Avicel pH 102, Talc, Lactose, ethanol

Article Info: Received 02 May 2019; Review Completed 14 June 2019; Accepted 21 June 2019; Available online 15 July 2019
Cite this article as:
Sharma SK, Patel RP, Enhancing the Solubility and Dissolution Rate of Meclizine Hydrochloride by Inclusion Complex
Journal of Drug Delivery and Therapeutics. 2019; 9(4):57-64 http://dx.doi.org/10.22270/jddt.v9i4.2981

*Address for Correspondence:

Sanjay Kumar Sharma, Department of pharmaceutical sciences, Pacific Academy of Higher Education and Research
University, Rajasthan, India

1.0 INTRODUCTION
Cyclodextrins (CD) inclusion complexation, which is the especially their solubility. The solubility of βCD in water is
arrangement of host–guest inclusion complexes by weak relatively low (approximately 18.5 mg/mL at 25 °C),
intermolecular interaction, has been shown to be a whereas it’s derivative HP βCD has a higher aqueous
promising technique in enhancing solubility and solubility (approx. 600 mg/mL at 25 °C). There are different
bioavailability of poorly BCS class II drugs. The molecular methods to prepare cyclodextrins inclusion complexes.
structure of cyclodextrins appears to be a truncated cone, These methods encompass co-precipitation, kneading,
arries a hydrophilic exterior surface and a non-polar interior lyophilization, spray drying, freeze drying and supercritical
cavity. The central cavity of the cyclodextrins molecule is fluid technology. Meclizine Hydrochloride is an Anti
lined with skeletal carbons and ethereal oxygens of the Histamine drugs. It is used mainly in the treatment of motion
glucose residues. It provides a Lipophilic microenvironment sickness and vertigo. The poor solubility of Meclizine
into which suitably sized API drug molecules may enter and Hydrochloride reduces the bioavailability to around 30 to
be included. This method has been shown to improve the 40%. Figure. 1 shows the chemical structures of Meclizine
solubility of various drugs such as celecoxib and natamycin Hydrochloride and βCD. In the present study, solubility and
etc. The commonly available cyclodextrins are, α-, β- and γ- dissolution enhancement of β-cyclodextrins (βCD) on
cyclodextrins, which consist of 6, 7 and 8 glucopyranose Meclizine Hydrochloride was compared. Inclusion complex
units, respectively. β-Cyclodextrins (β CD) and their was prepared using three different methods, namely,
derivatives, such as hydroxypropyl-βCD (HPβCD) and physical mixture, kneading and Co-precipitate method. The
methyl βCD (MβCD), are the main excipients commonly used inclusion complex was characterised using scanning electron
in pharmaceutical formulations. In general, chemical microscopy, infrared spectrophotometer, powder X-ray
modification of CDs can alter their physical properties, diffractometry, and differential scanning calorimetry.

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Sharma et al Journal of Drug Delivery & Therapeutics. 2019; 9(4):57-64

(A) (B)
Fig. 1 - Chemical structures of (A) Meclizine HCl (B) βCD
2.0
MATERIALS AND METHODS Preparation of complexes with β-cyclodextrin: 9,10,11
Materials: Meclizine Hydrochloride was a gift sample Complexes of Meclizine Hydrochloride with β-cyclodextrin
from Srikem Labatories Limited Mumbai. Other materials (β-CD) were prepared by different methods using different
were purchased from different sources like β Cyclodextrins molar concentrations of β-CD. The molar concentration used
from Gangwal chemicals Mumbai Lactose and Talc from and methods adopted are mentioned below.
signet chemicals, Mumbai, Micro crystalline cellulose PH
a) Physical mixture: Meclizine Hydrochloride with β-CD
102 and crosspovidone and ethanol from SR Chemi Mumbai
in different molar ratios (i.e. 1:1M, 1:2M and 1:3M) were
India and all other reagents used were of analytical grade
mixed in a mortar for about 30 minutes with constant
and obtained from S.D. Fine Chemicals, Mumbai, India.
trituration, passed through sieve No. 60 and stored in a
Doubled distilled water was used during entire research
desiccators over fused calcium chloride.
work.
b) Kneading method: Meclizine Hydrochloride with β-
Phase Solubility Studies: 6,7,8
CD in different molar ratios (i.e. 1:1M, 1:2M and 1:3M) was
The phase-solubility technique permits the evaluation of the taken. First cyclodextrin is added to the mortar, small
affinity between β-CD and Meclizine HCl in water. It gives quantity of 50 % ethanol is added while triturating to get
not only the solubilising ability of CD's, but also the stability slurry like consistency. Then slowly Meclizine Hydrochloride
constant of the complexes by analyzing the solubility curve. is incorporated into the slurry and trituration is further
Phase solubility studies were performed according to the continued for 30 minutes. Slurry is then air dried at 25 OC for
method reported by Higuchi and Connors. This methodology 4 hours, pulverized and passed through sieve No. 60 and
was based on the solubility variation of the guest molecule stored in desiccators over fused calcium chloride.
(drug) upon increase of the host molecule (β-CD/)
c) Co-precipitate method: Meclizine Hydrochloride was
concentration. For phase solubility studies of Meclizine
dissolved in ethanol at room temperature and β-CD was
Hydrochloride, an excess of drug (200 mg) was added to 20
dissolved in distilled water. Different molar ratios (i.e. 1:1M
ml portions of distilled water, each containing variable
1:2M and 1:3M of Meclizine Hydrochloride and β-CD were
amount of β-cyclodextrin such as 2, 4, 6, 8, and 10 m Moles.
taken respectively. The mixture was stirred at room
All the above solutions with variable amount of β-
temperature, for 30 minutes and then slowly evaporated on
cyclodextrins were shaken for 72 hours. After shaking,
a boiling water bath. The inclusion complex precipitated as a
approximately 0.5 ml of the solution was withdrawn by the
crystalline powder was pulverized and passed through sieve
syringe and filtered through a 0.22 μm membrane filter
No. 60 and stored in a desiccator till free from any traces of
(Millipore) and suitably diluted with water. Drug
the organic solvent.
concentration was determined spectrophotometrically using
(UV-1240, Shimadzu, Japan) at 230 nm. The phase solubility Sifted material Mix with other Prelubricant material and for
plot was prepared by plotting the total dissolved drug 10 minutes and then add Magnesium Stearate and mix for 2
concentration against the total β Cyclodextrin minutes.
concentrations separately. The apparent complexation
constant (K1:3) of the complex was calculated by the Differential Scanning Calorimetry (DSC) 12
following equation (Eq. 1) from phase solubility curve, DSC analysis was performed using a DSC 822e with a robotic
where the intercept is the intrinsic solubility of drug in the sampler from Mettler Toledo and thermal characteristics of
absence of polymer. the drug and solid dispersions were determined. The
instrument was calibrated using indium as the standard.
Approximately 5 mg of each sample was placed in 100 µL
K1:3 = Slope Eq. ------- (1) aluminum pans which were sealed and initial and final
temperature were set and heated from 25°C to 300°C at a
Intercept (1-slope)
rate of 10°C/min under nitrogen flow of 30 ml/min.

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Scanning electron microscopy In vitro dissolution studies 13

The surface morphology of the Meclizine Hydrochloride and The dissolution patterns of the inclusion complexes were
inclusion complex was determined using scanning electron compared with those of a market product. The dissolution
microscopy (LEO 435 VARIABLE PRESSURE SEM), operated studies were performed according to the USP XXIII
at an accelerating voltage of 20 kV (beam current of 30–40 Dissolution apparatus (ELECTROLAB TDL-08L), Type-I
mA, filament current of 1.75 lA, and probe current of 250 (Basket). The dissolution medium was 900 ml of 0.01N HCl
pA) Robinson detector and at magnification ranging from (pH 1.2). The stirring speed of the basket was 100 rpm, and
minimum magnification-4x and maximum magnification of the temperature was maintained at 37 ± 0.5°C. The samples
5000x. (5 ml) were withdrawn at various time intervals, which was
filtered through a 0.45 μm membrane filter and analyzed by
Fourier transform infrared spectroscopy 12,13 a HPLC spectrophotometer at 230 nm.
Fourier transform IR spectra were recorded on FT/IR-8400
Formulation of tablets by direct compression method 9,
S Shimadzu. The spectra were recorded for Meclizine HCl 10, 11
and inclusion complex system. Samples were prepared in a
KBr disc (3mg of the sample in 300mg KBr). The pinch of the Tablet compacts were prepared using a Fluid pack 10 ton
powder sample was inserted in the sample holder and the laboratory press 10.5 x 5.49 mm, Oval shaped Embossed
spectra were run from 3800 cm-1 to 650 cm-1. Tooling (Upper punches: Embossed with “ET3”, Lower
punches: plain). Tablets weighing 360 mg ± 5% were
compressed to 2 kN for 3 seconds and ejected from the die.

Table 1: Batches of Meclizine Hydrochloride Tablets by Inclusion Complex.

CD1 CD2 CD3 CD4 CD5 CD6 CD7 CD8 CD9
S.No Ingredients (mg) (mg) (mg) (mg) (mg) (mg) (mg) (mg) (mg)
Intra Granular Materials
Complex Ratio 1:1 1:2 1:3 1:1 1:2 1:3 1:1 1:2 1:3
1 Meclizine
25.0 25.0 25.0 25.0 25.0 25.0 25.0 25.0 25.0
Hydrochloride
2 β Cyclodextrins 58.8 117.6 176.4 58.8 117.6 176.4 117.6 176.4 58.8
3 Ethanol Q.s Q.s Q.s Q.s Q.s Q.s Q.s Q.s Q.s
4 Lactose regular 136.1 77.3 18.5 136.1 77.3 18.5 77.3 18.5 136.1
5 Microcrystalline
114.0 114.0 114.0 114.0 114.0 114.0 114.0 114.0 114.0
Cellulose PH 102
6 Crospovidone 20.0 20.0 20.0 20.0 20.0 20.0 20.0 20.0 20.0
7 Talc 3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0
Lubrication
8 Magnesium
3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0
Sterate
Weight of core tablet 360.0 360.0 360.0 360.0 360.0 360.0 360.0 360.0 360.0

Micromeritic properties of blend 12, 13, 14, 15, 16, 17, V10, V500 and V1250 to the nearest graduated unit. The Carr’s
Index is a measure of the propensity of a powder to be
The flow properties of powder plays vital role in the compressed and it is calculated using the following formula:
manufacturing of tablets. The flow properties were studied
through measuring the angle of repose, Carr’s index. Powder Carr’s Index = [(δtap -δb) / δtap] / ×100 Eq. ------- (3)
mixtures of different formulations were evaluated for angle
of repose, bulk density, tapped density Hausner’s Ratio and Evaluation of post compression parameters of tablets
compressibility index. It is usually determined by the fixed The prepared tablets were evaluated for tablet hardness
funnel method and is the measure of the flow ability of using a Monsanto Tablet tester, friability of a sample of 6.5 g
powder/granules. A funnel with 10 mm inner diameter of tablets was measured using a Roche Friabilator (Electro lab),
the stem was fixed at a height of 2 cm. Over the platform. the weight variation test was done by weighing 20 tablets
About 10 mg of sample was slowly passed along the wall of (USP) individually and calculating the average weight with
the funnel till the tip of the pile formed and touches the stem comparing the individual tablet weight to the average
of the funnel. A rough circle was drawn around the pile base weight, disintegration time of the tablet was measured in
and the radius of the powder cone was measured. Angle of water (37±2°C) according to the disintegration test
repose was calculated from the average radius, using the apparatus with a disk (Electro lab).
following formula.
3.0 RESULTS
Ө = Tan- [h/r] Eq. ------- (2)
Phase solubility study
In which, θ is the angle of repose, h is the height of the cone
and r is radius of base. To measure the angle of repose The solubility method is useful for studying inclusion
compounds for poorly soluble drugs with CDs in water
The bulk density (δb) of a powder was determined by because it gives not only the solubilizing ability of CDs but
measuring the volume of a known mass of powder sample also the stability constant (Ks) of the complexes by analyzing
into a 100 ml graduated cylinder. Tapped density (δtap) of the solubility curves.
powder samples were determined by a tap density
apparatus. Tap the cylinder 10, 500 and 1250 taps on the The phase solubility curves of Meclizine Hydrochloride in the
same powder sample and read the corresponding volume presence of ß-CD are presented in Figure.2. This curve
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Sharma et al Journal of Drug Delivery & Therapeutics. 2019; 9(4):57-64

indicated a linear increase in solubility of Meclizine Differential scanning calorimetry

Hydrochloride with increase in concentrations of β-CD in
Differential scanning calorimetry (DSC) was used to identify
water. Increasing amounts of β-CD increased the aqueous
solubility of Meclizine Hydrochloride. the inclusion complex between the drug and β-CD. Some
evidence of inclusion complexation was obtained from
The shape of solubility diagram represents linear host–guest thermal analysis. When guest molecules were embedded in
correlation (AL Type) with a slope less than 1 indicating the β-CD cavities, their melting, boiling, or sublimation point
formation of a 1:2 complex with respect to β-CD generally could shift to a different temperature or disappear
concentrations. It was observed that the Meclizine HCl/β-CD within the temperature range where β-CD was decomposed.
system shows greater solubility and this may be attributed to As seen from Figure 3, the DSC thermogram of Meclizine HCl
the fact that the contact surface and cavity size of β-CD thus, alone showed a sharp endothermic peak at 220.03 °C,
β-CD is selected for further formulation and evaluation corresponding to the melting point of the drug, while β-CD
studies. showed a very broad endothermic effect, which attained a
maximum around 86.06 °C, The endothermic peaks of
Phase Solubility at 250C y = 0.259x + 0.004 Meclizine HCl (205 °C) and β-CD (98.08 °C) observed in the
3 R² = 0.998
physical mixture were significantly different from their
Meclizine Hcl Solubility (mg/ml)

2.5 endotherms in pure forms (lowering of the endothermic

2
peak) indicating that complex formation has taken place only
partially that also indicates decrease in drug crystallinity due
1.5
to complexation. The same was the case for the complex
1 Series1 prepared by a co-precipitation method where endothermic
0.5 peaks of Meclizine HCl (185.26°C) and β-CD (99.11°C) were
observed which indicates complex formation is not complete
0
0 2 4 6 8 10 12 but has taken place to a greater extent. The complete
β Cyclodextrin conc (mM) disappearance of the Meclizine HCl endothermic peak was
observed for the inclusion complex prepared by the
kneading method Figure 4, since Meclizine HCl was
Fig.2: Phase Solubility curve of Meclizine Hydrochloride contained within the cavity of the β-CD ring molecule. This
with different concentration demonstrated that an inclusion complex of Meclizine HCl
could be obtained by the Kneading method.

Fig 3: DSC Thermogram of Meclizine Hydrochloride

Fig 4: DSC Thermogram of Meclizine Hydrochloride β CD inclusion Complex

Fourier transform infrared spectroscopy attenuated. The IR spectrum of the physical mixture could be
diagnosed as a superimposition of the bands of pure drug
IR spectrum of Meclizine HCl Figure 5 is characterized by and β-CD. Significant changes were recorded in the IR
2420cm-1 (–NH3– stretch), 2300cm-1 (CH2–CH2), 1450cm-1 (C
spectrum of the inclusion complex prepared by the kneading
= C stretch), 1080-1 (C–N stretch), 910 cm-1 (C–Cl stretch). Figure 6 Almost all peaks of Meclizine HCl were smoothened
The IR spectrum of pure b-CD is characterized by prominent
indicating a strong physical interaction between pure drug
peaks at 3410cm-1 (O–H), 2930.13cm-1 (C–H), 1620.73cm-
1(H–O–H bending), 1060.28cm-1 (C–O–C). No significant
and β-CD. However, the broad peak of O–H of β-CD was
consistently appeared in binary systems. All the binary
alterations in the IR bands of the pure drug were detected in
systems of Meclizine HCl-β-CD did not show any new peaks,
the physical mixture. However, some of the peaks of indicating non covalent interaction in inclusion complex.
Meclizine HCl were slightly shifted and found to be
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Sharma et al Journal of Drug Delivery & Therapeutics. 2019; 9(4):57-64

Fig 5: Infra Red Spectrum of Drug

Fig 6: Infra Red Spectrum of Drug Mix (CD)

Scanning electron microscopy produced from physical trituration method showed similar
surface morphology of mixtures of Meclizine Hcl and βCD
Fig shows the scanning electron photomicrographs of
Figure.7. No complexation occurred between Meclizine Hcl
Meclizine Hcl, βCD and physical mixture of Meclizine Hcl β-
and cyclodextrins using physical trituration method,
CD inclusion complexes prepared using the three methods.
indicating that inclusion complex could not be produced
βCD appears to be thick solid with non-smooth surface.
using physical trituration method. For kneading method,
Meclizine Hcl appears to be a solid with smooth surface. The there was formation Meclizine Hcl / βCD complex with
scanning electron photomicrographs of Meclizine Hcl β-CD
rough surface and irregular shape.

Meclizine Hydrochloride β CYCLODEXTRIN (PURE)

WIDTH =117.3μm WIDTH = 117.3μm

DETECTOR= ROBINSON
HEIGHT = 88 μm LENS =1000x DETECTOR= ROBINSON HEIGHT =88 μm
LENS =1000x DIMENSION=1024*768*8
20 μm DIMENSION 1024*768*8 20 μM

INCLUSION COMPLEX

WIDTH =46.93μm
DETECTOR= ROBINSON
HEIGHT =35.2 μm
LENS =2500x DIMENSION =1024*768*8
10 μm

Fig-7(A) scanning electron photomicrographs of pure Meclizine Hydrochloride (B) Beta Cyclodextrins. (C) Inclusion
Complex
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Drug content system (equivalent to about 50 mg of Meclizine HCl), were

dissolved in the mobile phase. The β-CD drug ratio would
The HPLC method with a UV-detector was used to determine
therefore remain 1:2] in the final solution to calculate the
the drug content of the binary system of the β-CD: Meclizine drug content. The potency content of drug in all the
HCl molar ratio of 1:2, in all system samples of the binary
formulation was found to be 97.0 to 101.0%.

Fig 8: chromatogram of Potency Assay

In vitro dissolution studies and up to 70% drug release in 45 min, whereas the Market
product exhibited the release of 81% in 10min and 97% drug
The release rate profile was drawn as the cumulative percent
release in 45 min. It was evident that the complex exhibited
release on the y-axis and time on the x-axis shown in Figure
the faster dissolution rate than Marketed Product. The very
9. It showed that the inclusion complex (CD5) of Meclizine
high increase of Meclizine HCl dissolution rate in the case of
HCl prepared by the kneading method released 75.5% drug
inclusion complex might be due to several reasons. The
in 10min, and up to 98.0% drug in 45 min while the inclusion formations of soluble inclusion complex are consequently
complex prepared by the co-precipitation method showed
solubility increase, better wettability and reduction of
70% drug release in 10min and up to 86 % drug release in
particle size.
45 min. Physical mixtures show release up to 50% in 10 min

Table 2: %Cumulative drug release

Time in %Cumulative drug release (Avg. ± RSD; n=6)
min
Innovator CD1 CD2 CD3 CD4 CD5 CD6 CD7 CD8 CD9

0 0 0 0 0 0 0 0 0 0 0

10 81.6±2.12 56.5±4. 64.8±2. 71.0±2. 74.6±1. 75.5±2. 74.4± 73.5± 72.0±1. 72.0±2.
65 69 41 64 07 2.96 2.51 83 91
20 93.8±1.04 65.3±4. 73.0±3. 79.0±1. 80.1±1. 80.0±1. 79.3± 78.9± 74.6±2. 81.4±2.
53 86 32 27 50 1.14 1.90 11 56
30 95.4±0.84 81.7±4. 84.2±2. 86.7±1. 85.3±1. 86.3±0. 86.2± 83.3± 79.8±0. 88.2±1.
15 27 62 62 76 1.61 2.05 56 35
45 97.2±0.74 87.3±1. 92.9±2. 93.6±1. 92.0±1. 98.0 92.7± 89.9 85.0±0. 93.7±2.
35 92 59 26 ±0.67 0.81 ±0.71 57 56
60 98.5±0.46 98.6±0. 99.6±0. 99.6±0. 99.7±0. 99.8±0. 98.7± 99.2± 93.1±0. 99.8±0.
70 69 95 57 47 0.63 0.48 71 93

Fig 9: Dissolution comparison between RLD and different IH formulation.

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Evaluation of precompression parameters of powder the batches were varied from 0.44 to 0.48 gm/ml and 0.60 to
blend 0.66 gm/ml, compressibility index of all the trial batches
ranged from 09.182% to 11.387% and the Hausner’s ratio of
The angle of repose of the powder blend (CD5) was found to all the batches prepared ranged from 1.106 to 1.126.
be 19.46°. The bulk density and tapped bulk density of all

Table 3: Flow characters and compressibility of the prepared formulation powder blends
Formulation Hausner’s
Bulk density Tapped density Carr’s Index Angle of repose
codes ratio
CD1 0.45±0.00 0.65±0.00 11.045 ± 0.46 1.127 ± 0.00 21.12 ± 0.55
CD2 0.44±0.02 0.63±0.00 11.387 ± 0.52 1.121 ± 0.01 19.32 ± 0.15
CD3 0.47±0.00 0.64±0.01 10.632 ± 0.61 1.112 ± 0.00 24.52 ± 0.36
CD4 0.45±0.00 0.62±0.01 11.281 ± 0.74 1.126 ± 0.01 22.35 ± 0.25
CD5 0.48±0.01 0.62±0.01 09.812 ± 0.54 1.106 ± 0.01 19.46 ± 0.74
CD6 0.45±0.01 0.66±0.01 11.274 ± 0.32 1.125 ± 0.01 24.12 ± 0.23
CD7 0.44±0.00 0.62±0.00 10.097 ± 0.44 1.118 ± 0.01 23.38 ± 0.45
CD8 0.44±0.01 0.60±0.01 09.182 ± 0.68 1.109 ± 0.01 19.28 ± 0.81
CD9 0.42±0.00 0.71±0.00 12.112 ± 0.61 1.119 ± 0.00 22.12 ± 0.36

Evaluation of postcompression parameters of tablets of ±7.5%. The in vitro dissolution studies showed that almost
75.5% of the drug was released within 10min and almost
The hardness of the prepared tablet (CD5) was found to be
98.0% of the drug was released at the end of 45min. The
10.08±0.60 kg/cm2. Friability was found to be 0.0%, which
prepared tablets were compared with the marketed tablet,
were below 1% indicating sufficient mechanical integrity and the dissolution parameters of both formulations are
and strength of prepared tablets. The disintegration time
shown in Table 4 and Figure 10. The drug content was found
was found to be 02:50 to 04:02. Weight variation was found
to be 99.5%.
to be 365.0±0.92 mg which was within the permissible limit

Table 4: Results of evaluation tests of Meclizine Hydrochloride tablets of all formulations

Formulation Hardness Average Weight Disintegration time Friability (%)
code 2 (mg) (minute: second)
(Kg/cm )
CD1 9.75±0.74 362.0±1.04 04:02 to 05:20 0.1
CD2 10.30±0.79 364.0±0.62 03:25 to 04:54 0.2
CD3 9.92±0.73 362.0±1.07 02:18 to 07:09 0.0
CD4 9.95±0.67 363.0±1.21 01:38 to 02:30 0.0
CD5 10.08±0.60 365.0±0.92 02:50 to 04:02 0.0
CD6 9.87±0.69 364.0±1.26 01:48 to 02:06 0.0
CD7 9.93±0.71 361.0±0.82 02:55 to 04:50 0.0
CD8 9.58±0.56 359.0±1.06 03:57 to 04:49 0.0
CD9 9.33±0.22 361.0±1.11 04:21 to 06:01 0.1

Graph Between Different Trials of Weight Variation Graph Between Different Trials of Hardness Variation

380 12
% Hardness Variation
% Weight Variation

370 11

360 10

350 9

340 8
1

9
D

D
C

No of Trials No of Trials

Fig 10: Graph Between different trials of (A) Weight variation (B) Hardness variation

4.0 DISCUSSION flattening of endotherm which indicates the formation of

true complex and conversion of a drug-to-amorphous form.
From the result it is observed that the solubility of Meclizine The dissolution rate increase for the physical mixture,
HCl in the presence of β-cyclodextrin can be classified as the kneaded and co-precipitation mixtures is due to the wetting
AL type. This indicated that the complexes at 1:2 ratios are effect of the β-CD, this effect is more evident for the kneaded
adequately stable and also the extent of solubility product, where the mixing process between the two
enhancement being higher for β-CD. While the DSC components is more intensive. The effect of complexation
thermogram of the kneading complex shows the complete with β-CD on the solubility of Meclizine HCl can be explained
disappearance of the Meclizine HCl endothermic peak and in terms of the reduction in the crystallinity of the drug and
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Sharma et al Journal of Drug Delivery & Therapeutics. 2019; 9(4):57-64

conversion to amorphous form by inclusion into the characterization, inclusion mode, and solubilization.
hydrophobic cavity of the β-CD. Carbohydrate Polymers 2011; 85:629–637.
2. Loftsson T, Brewster M E et al. Pharmaceutical applications of
The FTIR spectra for Meclizine Hcl and the optimum formula cyclodextrins Drug solubilisation and stabilization. J Pharm Sci
showed the main characteristic absorption bands of 1996;85:1017–1025.
functional groups of C-CL, C-N amine and C=C stretching . As 3. Singh R, Bharti N, Madan J, et al. Characterization of
shown in characteristic absorption peaks of Meclizine cyclodextrins inclusion complexes – a review. J Pharm Sci
Technology 2010; 2:171–183.
Hydrochloride appear almost at the same region. These
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