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Formulation and evaluation of vilazodone sublingual tablets by using

lyophilization technique

Article  in  Research Journal of Pharmacy and Technology · January 2018

DOI: 10.5958/0974-360X.2018.00050.1

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 Research J. Pharm. and Tech. 11(1): January 2018

ISSN 0974-3618 (Print) www.rjptonline.org

0974-360X (Online)

RESEARCH ARTICLE

Formulation and evaluation of vilazodone sublingual tablets by using

lyophilization technique
K. C Panda 1*, A. V Reddy2, N. Panda2, MD Shamim2, M. Habibuddin3, K.N Jayaveera4
1
Research scholar, JNTUA, Ananthapuramu, Andhra Pradesh
2
Anwarul Uloom College of Pharmacy, New Mallepally, Hyderabad, Telangana.
3
Adept Pharma and Bioscience Excellence, Balanagar, RR Dist., Telangana.
4
VEMU Institute of Technology, P. Kothakota, Chittoor, Andhra Pradesh
*Corresponding Author E-mail: kanhuchpanda@gmail.com

ABSTRACT:
Vilazodone is approved for treatment of acute episodes of major depression (Major Depressive Disorder (MDD).
It is a BCS Class – II drug, offer challenges in developing a drug product with adequate bioavailability. The aim
of present investigation was to formulate and evaluate vilazodone sublingual tablets using poloxamer 407 as a
carrier by lyophilized solid dispersion technique.The lyophilized solid dispersion of vilazodone prepared by
poloxamer 407 (1:5) showed more than 85% drug release within 5 min, so it was used for the development of
sublingual tablets by direct compression technique. The physicochemical, solid-state properties, dissolution
behaviour of lyophilized solid dispersion as well as sublingual tablets were evaluated. Finally, the bioavailability
studies of the prepared tablets were performed by sublingual administration to rabbits. The sublingual tablets
showed a higher in vitrodis solution rate and bioavailability compared with the commercial tablets. It is evident
from the results herein that the developed sublingual tablets provide a promising drug delivery system in drug
development, owing to their excellent performance of a rapid onset of action and improved bioavailability.

KEYWORDS: Vilazodone, lyophilization, sublingual, dissolution.

INTRODUCTION: It acts as a serotonin reuptake inhibitor and 5HT1A

Drug delivery through the sublingual route had emerged receptor partial agonist [3-5]. It increases serotonin levels
from the desire to provide immediate onset of in the brain by inhibiting the reuptake of serotonin while
pharmacological effect. Dysphasia (difficulty in acting as a partial agonist on serotonin-1A receptors.
swallowing) is a common problem of all age groups,
especially geriatrics, paediatric, and patients who are It has therefore been coined by scientists as a selective
mentally retarded, uncooperative, nauseated or on partial agonist and reuptake inhibitor (SPARI). Because
reduced liquid intake/diets have difficulties in of its partial agonist activity for serotonin-1A,
swallowing these dosage forms. Sublingual means under vilazodone helps to reduce anxiety. It is extensively
the tongue. Drugs that are given sublingually reach metabolized by liver, through CYP and non- CYP
directly in to the systemic circulation through the ventral pathways (major: CYP3A4, minor: CYP2C19 and
surface of the tongue and floor of the mouth. The drug is CYP2D6)[6-9].
rapidly absorbed into the reticulated vein that lies
underneath the oral mucosa[1-2]. Vilazodone is approved It is a BCS Class - II drug, offer challenges in developing
for treatment of acute episodes of major depression a drug product with adequate bioavailability [10]. The aim
(Major Depressive Disorder (MDD). of present investigation was to formulate and evaluate
vilazodone sublingual tablets using poloxamer 407 as a
carrier by lyophilized solid dispersion technique to
Received on 08.11.2017 Modified on 24.11.2017
Accepted on 19.12.2017 © RJPT All right reserved bypass first pass metabolism, owing to their excellent
Research J. Pharm. and Tech. 2018; 11(1): 267-274. performance of a rapid onset of action and improved
DOI: 10.5958/0974-360X.2018.00050.1 bioavailability.
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 Research J. Pharm. and Tech. 11(1): January 2018

MATERIAL AND METHODS: and volume was made up to 100 ml with methanol and 1
Materials: ml of this solution was taken and it was diluted to 10 ml
Vilazodone was gifted by Dr. Reddy's Laboratories Ltd., with methanol and absorbance was noted at 240 nm,
Hyderabad, poloxamer 407 purchased from S.D. Fine concentration of vilazodone was determined using
Chemicals Ltd. All other chemicals used were of calibration curve of vilazodone in methanol.
analytical grade and procured from commercial sources.
Percentage yield value:
Phase solubility analysis: The Percentage yield value of solid dispersions and
The effect of concentrations of Poloxamer 407 on the physical mixtures were measured by the following
equilibration solubility of vilazodone in water and pH formula.
6.8 phosphate buffer medium at room temperature was Percent yield value= (Practical yield value / Theoretical
carried out by adding an excess quantity of drug (20 mg) yield value) X 100
into a screw-capped glass vial containing 20 ml of
solvent with various concentrations of the carrier. The Characterization of solid dispersion:
suspension were shaken for 24hrs on a rotary bath shaker Fourier transform infrared spectroscopy (FT-IR):
and filtered through Whatman no.1 filter paper. The The FT-IR spectra were obtained using FT-IR
filtrate so obtained was diluted and analyzed spectrometer (Shimadzu).The samples were previously
spectrophotometrically at 240 nm[14]. For determination ground and mixed thoroughly with potassium bromide,
of spontaneity of the process, the values of Gibbs free an infrared transparent matrix in 1:5 (sample: KBr) ratio,
energy (ΔGtr) were calculated for each carrier. respectively. The KBr discs were prepared by
compressing the powders at a pressure of 5 tons for 5
Preparation of physical mixtures and solid min in a hydraulic press. Forty five scans were obtained
dispersions: at a resolution of 4 cm1 from 4500 to 400 cm1.
Physical mixtures were prepared by mixing of
vilazodone and poloxamer 407 in mortar and pestle Differential Scanning Calorimetry:
according to 1:1, 1:3, 1:5 ratios by geometrical dilution The DSC measurements were performed on a Pyris
method and coded as VZD-PXM 407 Pm1:1, VZD-PXM Diamond TG/DTA differential scanning calorimeter
407 Pm1:3, VZD-PXM 407 Pm1:5 respectively. The with thermal analyzer. All accurately weighed samples
geometric mix blends passed through sieve no#60 and (about 5 mg) were placed in sealed aluminium pans. An
kept in the desiccator [12-13]. empty aluminium pan was used as reference.

Vilazodone and the hydrophilic polymer PXM 407were X-ray diffraction:

weighed according to 1:1, 1:3, 1:5 ratios and coded as The X-ray powder diffraction patterns were obtained by
VZD-PXM 407 Lyo1:1, VZD- PXM 407 Lyo 1:3 VZD- using Philips Holland PW 1710 with Cu K ( =
PXM 407 Lyo1:5 respectively. Specified quantity of 1.54056Ao) radiation and a crystal monochromator,
drug was weighed and dispersed into 100 ml poloxamer voltage: 45 mv and current: 20 amps. The diffraction
solution. The dispersion being stirred with the help of patterns were run at 20/min in terms of 2 angle.
magnetic stirrer, to this 25% liquid ammonia added drop
wise and stirred until a clear solution was obtained. Then In-vitro Dissolution rate studies:
the samples were transferred into glass vials and The in vitro dissolution studies of physical mixtures and
incorporated to the ports of lypholizer with closed mode solid dispersions of vilazodone were carried out on USP
of valves and frozen at a temperature of -40°C for 3 type II dissolution apparatus and the results were
hours. Then the valves of lypholizer were opened slowly compared with those for pure vilazodone. The dissolu-
and the samples were sublimed under a pressure of 0.09 tion vessels contained 900 mL of phosphate buffer pH
mbar and with a condenser temperature of -40°C for 12 6.8 maintained at 37°C ± 0.5°C and paddle speed set at
hours followed by a secondary drying at 25°C for 2 50 rpm. Solid dispersions equivalent to 20 mg of
hours using Yorco Freeze Dryer-Lypholizer. The frozen vilazodone were added to the dissolution medium in a
dried mass was passed through sieve no. #60 to get fine powder form. Then, 5 mL samples were withdrawn at 5,
powders and kept in desiccators[15-18]. 10, 20, 30, 45 and 60 min from the dissolution medium.
The withdrawn sample was replenished with 5 mL of
Analysis of drug content in solid dispersions: fresh media. The withdrawn samples were analyzed for
The drug content of vilazodone in each physical vilazodone content by measuring the absorbance at 240
mixtures and solid dispersions were determined using nm using UV-visible spectrophotometer (Shimadzu).
UV-spectroscopy. Accurately weighed quantity of solid Dissolution studies for each formulation were performed
dispersion or physical mixture equivalent to 10 mg of in triplicates.
vilazodone was transferred to 100 ml of volumetric flask
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 Research J. Pharm. and Tech. 11(1): January 2018

Preparation of sublingual tablets: flat punch. The sublingual tablets of vilazodone were
The lyophilized solid dispersion VZD-PXM 407 Lyo1:5 prepared by direct compression using Polyplasdone XL
showed the maximum solubility and dissolution rate was 10 (VF9 – VF12) and Ac-Di-Sol (VF13 – VF16) as
selected for preparation of sublingual tablets given in superdisintegrants with two control formulations (VC3–
table 1.All the ingredients were mixed geometrically and VC4).
subjected for direct compression using 8mm embossed
Table 1: Formulation table of vilazodone sublingual tablets
Formulation Batches
Drug and Excipients(mg) VF9 VF10 VF11 VF12 VF13 VF14 VF15 VF16 VC3 VC4
Vilazodone Equivalent To 10 mg(Lyo Polo 407 1:5) 60 60 60 60 60 60 60 60 --- ---
Vilazodone --- --- --- --- --- --- --- --- 10 10
Poloxamer 407 --- --- --- --- --- --- --- --- 50 50
Avicel PH 112 47 32 22 13 29 22 15 8 13 8
Pearlitol SD 200 32 45 51 58 50 55 58 63 58 63
PVP K 30 5 5 7 7 5 5 7 7 7 7
Polyplasdone XL 10 2 4 6 8 --- --- --- --- 8 ---
Ac-Di-Sol --- --- --- --- 2 4 6 8 --- 8
Aspartame 1 1 1 1 1 1 1` 1 1` 1
Magnesium Stearate 2 2 2 2 2 2 2 2 2 2
Talc 1 1 1 1 1 1 1` 1 1` 1
Total tablet weight 150mg

Characterization of the prepared sublingual tablets: withdrawn at 5, 10, 20, 30, 45 and 60 min from the
Formulated vilazodone sublingual tablets were subjected dissolution medium. The withdrawn sample was
to different physical characterization studies. Weight replenished with 5 mL of fresh media. The withdrawn
variation test was done by weighing 20 tablets samples were filtered and analyzed for vilazodone
individually, calculating the average weight and content by measuring the absorbance at 240 nm using
comparing the individual tablet weight to the average UV-visible spectrophotometer (Shimadzu). Dissolution
weight. The tablet hardness was determined using studies for each formulation were performed in
Monsanto tablet hardness tester and friability was triplicates. In order to evaluate the similarity between the
determined Roche friabilator. The disintegration time best formulation and marketed formulation(MKF), the in
was measured by using tablet disintegrator (Electrolab, vitro dissolution profiles of both were compared[21-
22]
India). Wetting time and dispersion were determined by .The similarity factor is stated as logarithmic
well reported method. The uniformity of the drug conversion of the sum squared error of differences
content in tablets was evaluated by determining the between the test formulations and reference formulation
contents of 3 tablets individually and analysed which is calculated by the using following equation:
spectrophotometrically. Moisture uptake studies were
carried out by taking ten tablets from each formulation
were kept in a desiccator over calcium chloride at 37°C
for 24 h. Then the tablets were weighed and exposed to
Difference factor (f1) measures the percent error between
75% relative humidity (using saturated sodium chloride
the drug release profiles of two formulations, usually one
solution) at room temperature for 4 weeks. Tablets
is test and other is standard over predetermined time
prepared by without lyophilization technique chosen as
points. The formula used to calculate the difference
control formulations were kept to assess the moisture
factors is presented as following equations.
uptake due to other excipients. Tablets were weighed
and the percentage increase in weight was recorded [19-20].
In vitro Release Studies of vilazodone sublingual
tablets: In Vivo Bioavailability Studies:
The release rate of sublingual tablets containing control Six healthy male New Zealand white rabbits were
formulations (VC3and VC4 ) prepared by without housed under standard conditions and allowed free
lyophilization technique, lyophilized solid dispersion of access to food and water. All rabbits were dosed
vilazodone (VF12), and marketed formulation(containing following an overnight fasting; Food was returned 2 h
equivalent of 10 mg of vilazodone) was determined after dosing. Rabbits were used as animal model for in
using USP type II apparatus (Paddle method). The vivo study and permission for laboratory animal was
dissolution test was performed using 900 mL of approved by IAEC (IAUCP/IAEC/2016/11/PN-02). The
phosphate buffer pH 6.8 maintained at 37°C ± 0.5°C and study was conducted by using parallel design. Six rabbits
paddle speed set at 50 rpm. Then, 5 mL samples were were randomly divided into two groups. One group

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 Research J. Pharm. and Tech. 11(1): January 2018

received the marketed formulation viibryd10 (containing RESULTS AND DISCUSSION:

10 mg vilazodone), whereas the other group received Phase solubility study:
optimized sublingual tablets (VF12). During the drug Using the highest carrier concentration, the solubility
administration, an operator placed each rabbit in a body increased approximately 6.28 fold in distilled water and
restraint device, which exposed the animal’s head, and 6.29 fold in pH 6.8 phosphate buffer as compared to pure
lifted apart the gums with a wooden tongue depressor. drug. The solubility found in this study for vilazodone at
Subsequently, sublingual tablets were placed under the 25ºC was 0.132 mg/mL in distilled water and 0.141
rabbit’s tongue, wetting with 3 mL of water. At the same mg/mL in pH 6.8 phosphate buffer. The values of Gibbs
time, wooden rod was placed to prevent chewing or free energy (ΔGtro) associated with the aqueous
swallowing the tablet. Rabbit blood samples were solubility of vilazodone in presence of carrier were all
obtained from the ear marginal vein before negative at various concentrations, indicating the
administration and at predetermined time intervals after spontaneous nature of drug solubilisation. The values
administration (0.5, 1, 2, 3, 4, 8, 16 and 24 h) then stored decreased with increasing carrier concentration,
in heparinised tubes. Plasma samples and deproteinizing demonstrating that the reaction became more favourable
solution were mixed in a ratio of 4:1 and added to a 2 ml as the concentration of carrier increased.
polypropylene micro centrifuge tube. After capping, the
tube contents were vortex mixed for 30 seconds, and the Percent Yield and Drug Content:
suspension is centrifuged at 4000 rpm for 10 minutes The percent yield of various vilazodone physical
and then stored at -70°C for further analysis. Plasma was mixtures and solid dispersions was within the range of
partitioned using micropipette for quantitative estimation 90.56 % to 99.02 %. The percentage drug content in
of drug.). The supernatant liquid was collected and physical mixtures and solid dispersions was within the
diluted with the mobile phase; was analyzed by RP range of99.89±0.21 % to 99.45±0.65 % and 97.95±0.24
HPLC method. For the HPLC instrument BDSC18 % to 98.96±0.45 respectively. This indicated that drug
column (250×4.6 mm, 5µ) was used for the analysis. The was uniformly distributed in all of these prepared
mobile phase combination used for the assessment of physical mixtures and solid dispersions the percent yield
vilazodone in the rabbit plasma was combination of more in case of physical mixtures than solid dispersions.
Acetronitrile: Phosphate buffer (12.5 mM potassium
dihydrogen orthophosphate) pH 3 in the ratio of 18:82. Solid state characterization study:
The flow rate was regulated with 1 ml/min. The FTIR Spectroscopy Analysis:
detection was carried out at 240 nm with UV FTIR spectra of pure vilazodone, poloxamer 407 and
spectroscopic detector. physical mixture are shown in Figure 1. The
The pharmacokinetic parameters such as maximum characteristic peaks of pure vilazodone were found at
plasma concentration (Cmax), time for peak plasma 3437cm-1 (NH stretching), 3216 cm-1 (Aromatic C-H
concentration (tmax), plasma half-life (t½), area under stretching ), 2939 cm-1 (Aliphatic C-H stretching), 2217
curve [AUC(0-t)] and mean residence time (MRT)were cm-1 (C≡N stretching), 1669 cm-1 (C=O stretching),
calculated using by Kinetica 5.0 software[23]. 1575&1443 cm-1 (C=C ring stretching). The intensity
peaks of vilazodone were found to be present in the
Accelerated stability studies: spectra of physical mixture with poloxamer 407. This
The stability studies were carried outfor optimized finding reveals the lack of interaction between the drug
vilazodone sublingual tablets (VF12) according to ICH and the carrier in the sample.
guidelines for three months at accelerated temperature
40 ± 2°C/75 ± 5% RH. The tablets were withdrawn at an
interval of 30 days, 60 days and 90 days for evaluation in
vitro drug release characteristics.

Fig. 1 (A) FTIT spectra of vilazodone, (B) Poloxamer 407, (C) VZD-PXM 407 physical mixture

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 Research J. Pharm. and Tech. 11(1): January 2018

DSC Analysis: DSC curve of lyophilized solid dispersion showed

The DSC thermogram of pure vilazodone showed a reduction in melting point of drug to 173.5°C with
sharp endothermic peak at 202.1°C, corresponding to its widening of peak. This reduction in melting point and
melting point. The DSC curve of physical mixture of broadening of peak was an indication of conversion of
VZD with poloxamer 407 showed the endothermic peaks crystalline fraction of drug into amorphous one. The
at 202.1°C and 65.7°C which are the corresponding DSC thermograms are shown in Figure 2.
melting point of drug and polymer respectively. The

Fig. 2 (A) DSC thermogram of vilazodone, (B) VZD-PXM 407 physical mixture, (C) VZD-PXM 407 lyophilized SD

X-ray diffraction: distinct peaks but lyophilized solid dispersion prepared

X-ray diffraction spectra of pure vilazodone, physical with poloxamer 407 showed a reduction in the total
mixture and solid dispersion are illustrated in Figure 3. number of peaks and base broadening of appeared peak
The presence of sharp distinct peaks in vilazodone along with a reduction in peak intensity providing
spectra indicated its high crystallinity. The diffraction convincing evidence for the formation of amorphous
spectrum showed that the drug in crystalline form as form in solid dispersion. The result indicated that the
demonstrated by numerous distinct peaks at 2θof 8.41, drug in solid dispersion was in amorphous form. Hence,
9.007, 12.09, 16.803, 18.899, 20.99, 21.879, 24.54, VZD-PXM 407 Lyo1:5 showed the maximum solubility
25.69, 26.14, 28.16 and 29.52. The spectrum physical and dissolution rate was selected for preparation of
mixture prepared with poloxamer 407 showed numerous sublingual tablets.

Fig. 3 (A) XRD Patterns of vilazodone, (B) VZD-PXM 407 physical mixture, (C) VZD-PXM 407 lyophilized SD

In-vitro Dissolution rate studies: dissolution than their respective physical mixture
The in vitro dissolution profiles of the drug, various solid samples. This observation indicated that the increased
dispersions using poloxamer 407 and their respective dissolution of vilazodone from lyophilized solid
physical mixtures in phosphate buffer (pH = 6.8) are dispersion due to presence of drug in amorphous state as
shown in figures 4(A) and 4(B). All of the physical compared to the physical mixtures and pure drug, where
mixture and solid dispersion samples showed improved drug is present in crystalline state. The pure drug
dissolution of vilazodone. Again, all of the solid showed up to 50% dissolution over 60 min, but its solid
dispersion samples showed more improved vilazodone dispersions prepared by lyophilization technique with

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 Research J. Pharm. and Tech. 11(1): January 2018

poloxamer 407 (VZD-PXM 407 Lyo1:5) showed the within 10 min. Hence, VZD-PXM 407 Lyo1:5 was
maximum solubility and dissolution rate at94.89% selected for preparation of sublingual tablets.

Fig. 4: In-vitro drug release profiles of vilazodone from (A) Physical mixtures, (B) Solid dispersion

Characterization of the prepared sublingual tablets: weight of the prepared tablets was in range of 147 to 151
Solid dispersions prepared by lyophilization technique and hardness of prepared tablets was in between 3.0 to
with poloxamer 407 (VZD-PXM 407 Lyo1:5) showed 3.5 kg/cm2. The friability of all the formulations was less
the maximum solubility and dissolution rate. So it was than 1% indicating the ability of tablet to withstand
selected for preparation of sublingual tablets. The abrasion in handling packaging and shipment. The drug
sublingual tablets of vilazodone were prepared by direct content of the prepared formulations was found to be
compression using Polyplasdone XL 10 (VF9 – VF12) between 96.89% and 98.83% which was found within
and Ac-Di-Sol (VF13 – VF16) as superdisintegrants with pharmacopoeia limits. The formulationVF12prepared by
two control formulations (VC3–VC4). Avicel PH 112 lyophilization technique containing Polyplasdone XL 10
was used as directly compressible diluent as less (5.33%) as superdisintegrant showed least wetting time,
compression force is required to produce tablets of a disintegration time and in-vitro dispersion time
given hardness. It has very low moisture content (1.5%); compared to other formulations due to its smaller,
so used in preparation of moisture sensitive lyophilized porous and granular particles which exhibit high
sublingual tablets. Pearlitol SD 200was also used capillary activity and pronounced hydration capacity,
directly compressible diluents as it imparts with little tendency to form gels. All sublingual tablets
multidimensional benefits as it has excellent aqueous showed good stability when exposed to 75% relative
solubility, nonhygroscopicity and wetting properties humidity and final % increase in weight ranged from
facilitating tablet breakdown as well as negative heats of 1.3% to 2.4% due to use of nonhygroscopic excipients
solution. The slight bitter taste of the drug has been for formulation of sublingual tablets. The results of
masked by using 0.66 % w/w of aspartame. The average prepared sublingual tablets were presented in table 2.

Table 2: Evaluation of post compression parameters of Vilazodone sublingual tablets from formulation VF9 – VF16
Formula- Weight Hardness Friability Wetting Disintegration Invitro Drug % Increase
tion code variation kg/cm2 (%) time Time (Sec) dispersion content in weight
(mg) (Sec) time(Sec) (%) (after 4
weeks)
VF9 149±0.34 3.00±0.25 0.75±0.03 22.43±0.56 17.12±0.12 31.88±0.14 98.34±0.81 1.7±0.03
VF10 149±1.05 3.00±0.25 0.73±0.02 16.77±0.13 14.07±0.11 29.69±0.13 96.89±0.83 2.1±0.08
VF11 148±1.04 3.50±0.25 0.41±0.02 14.88±0.09 12.05±0.18 25.51±0.15 97.86±0.39 1.9±0.05
VF12 151±1.67 3.50±0.15 0.38±0.01 13.86±0.14 10.11±0.12 22.62±0.15 98.25±0.72 1.6±0.11
VF13 151±0.95 3.00±0.15 0.70±0.03 35.65±0.87 29.06±0.13 39.08±0.14 97.45±0.32 2.4±0.09
VF14 151±0.96 3.00±0.25 0.66±0.02 27.65±0.65 24.08±0.21 30.17±0.15 98.83±0.88 2.2±0.05
VF15 148±0.85 3.25±0.15 0.63±0.02 22.99±0.54 19.10±0.14 27.45±0.16 97.76±0.39 2.0±0.08
VF16 147±0.68 3.50±0.25 0.57±0.01 19.64±0.23 16.10±0.23 21.72±0.19 98.15±0.72 1.9±0.03
VC3 151±0.95 3.5±0.25 0.26±0.01 57.99±0.23 39.11±0.12 69.45±0.16 97.99±0.74 1.3±0.06
VC4 151±0.78 3.0±0.25 0.23±0.03 58.92±0.96 37.08±0.34 65.72±0.19 98.64±0.81 1.5±0.15
All values are expressed as mean± SD; (n=3)

In vitro release studies of vilazodone sublingual viibryd10 (MKF) and control formulations (VC3–VC4)
tablets: given in Fig 5. The extent of dissolution of vilazodone
The dissolution profiles of vilazodone sublingual tablets from the marketed formulation was 90.15% in 20 min.
prepared by lyophilized solid dispersion technique (VF9- The control formulationsVC3and VC4 prepared without
VF16) compared with the marketed formulation lyophilization technique showed 73.92% and 71.55% in
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 Research J. Pharm. and Tech. 11(1): January 2018

60 min respectively. Hence, the lyophilized solid prepared by lyophilization technique containing
dispersion VZD-PXM 407 Lyo1:5 showed the maximum Polyplasdone XL 10 as superdisintegrant showed more
solubility and dissolution rate was selected for percentage of drug release than the sublingual tablets
preparation of sublingual tablets. All formulae showed containing Ac-Di-Sol. The in vitro dissolution results of
acceptable dissolution rate. The formulationVF12 all the batches of prepared sublingual tablets were
prepared by lyophilization technique containing compared with dissolution results of marketed
Polyplasdone XL 10 (5.33%), Pearlitol SD 200(38.66%) formulations by calculating the similarity factors (f2) and
and Avicel PH 112 (8.66%) w/w showed the highest difference factors (f1). Control formulations VC3 and
percentage of drug release 93.98% within 5 minutes; this VC4 showed dissimilarity in the dissolution profile
may be due to faster uptake of water owing to the porous whereas all formulations such VF9 to VF16 showed
structure formed. It could be attributed to the formation similarity in the dissolution profile. Among all the
of porous structure in lyophilized tablets in addition to formulations, VF13 showed highest f2 value (61.31) and
incorporation of water soluble excipients. The tablets lowest f1 value (1.31).

Fig. 5 (A): Comparative in-vitro drug release profiles of vilazodone sublingual tablets (VF9 – VF12), control formulation (VC3) and
marketed formulation
Fig. 5 (B) Comparative in-vitro drug release profiles of vilazodone sublingual tablets (VF 13 – VF16), control formulation (VC4) and
marketed formulation

In Vivo Bioavailability Studies: Table 3: Pharmacokinetic parameters of optimized and marketed

formulations
The in vivo pharmacokinetic parameters for the
Pharmacokinetic Marketed Optimised
optimized sublingual tablets (VF12) along with marketed parameters formulation formulation
formulation were performed in male New Zealand white (VF12)
rabbits. The in vivo data for both the formulations were Cmax (ng/ml) 118.43±0.25 120.56±0.12
compared and represented in table 3. The plasma levels tmax (hour) 4.08 ±0.10 2.10 ±0.11
of vilazodone after sublingual administration of VF12 AUC0-t (ng-hour/ml) 2176.45 2206.23
were clearly faster and higher than those of the AUC0-∞ (ng-hour/ml) 2235.83 2386.12
commercial tablets. In particular, the tmax after the MRT (hour) 14.47 15.21
administration of marketed formulation was observed at
4.08h; However, sublingual tablets (VF12) resulted in the Accelerated stability studies:
rapid appearance of vilazodone in plasma, attaining the The stability studies were carried out for optimized
Tmax after 2.1h. In addition, the peak plasma vilazodone sublingual tablets (VF12)according to ICH
concentration (Cmax) for viibryd10 and test (VF12) were guidelines for three months at accelerated temperature
found 118.43±0.25and 120.66±0.12ng/ml 40 ± 2°C/ 75 ± 5% RH. The stability studies indicated
respectively.The differences between the two that there was no significant change observed for in vitro
formulations for Tmax were statistically significantly dissolution studies after three months. Vilazodone
different having P value 0.0003 (P< 0.05) but in case of sublingual tablets (VF12) were found to be stable for the
Cmax there was no significant different found, having P period of three months at 40°C ±2°C/75% RH ± 5%.
value 0.5559 (P < 0.05). These results indicated that the
onset of action of vilazodone from optimized sublingual
tablets (VF12) is reaching much earlier than the marketed
formulation.
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CONCLUSION: 15. Tsinontides SC, Rajniak P, Hunke WA, Placek J, Reynolds SD.
Freeze drying‐principles and practice for successful scale‐up to
Solid dispersions prepared by lyophilization technique manufacturing. Int J Pharm. 280(1); 2004: 1‐16.
with poloxamer 407 (VZD-PXM 407 Lyo1:5) showed 16. Bandry MB, Fathy M. Enhancement of the dissolution and
the maximum solubility and dissolution rate. So it was permeation rates of meloxicam by formation of its freeze‐dried
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