INTRODUCTION:

Solubility of drugs is a major concern in the design of pharmaceutical formulations lead

to variable bioavailability. Poorly water‐soluble drugs are associated with slow drug absorption
leading eventually to inadequate and variable bioavailability. The rate limiting step for most of
the pharmaceutical formulations is dissolution1.
In order to enhance the bioavailability of poorly water-soluble drugs, an increasing
number of pharmaceutical formulation technologies are being developed to address this
challenge of drug product development. These include solid dispersions. The therapeutic usage
of solid dispersions has been the focus of many recent studies and several successful examples
have been commercialized in pharmaceutical market. In solid dispersions drug molecules or
very fine drug crystals are dispersed in a biocompatible or water-soluble matrix. A number of
watersoluble polymers such as hydroxypropylcellulose, hydroxypropyl methylcellulose (HPMC),
polyethylene glycol (PEG), and poly(vinylpyrrolidone) (PVP) have been used as carriers for solid
dispersions.2

Bicalutamide
Bicalutamide is propanamide, N‐ [4‐cyano‐3‐ (trifluoromethyl) phenyl]‐3‐[(4‐
fluorophenyl) sulfonyl]‐2‐hydroxy‐2‐ methyl‐propanamide. It is poorly soluble drug which is
non-steroidal androgen (pKa 12). Aqueous in vitro solubility of bicalutamide is low at 5 μg/mL
at pH 7 and 37°C.3
In addition, formation of solid dispersions (SDs) with hydrophilic carriers [povidone K 30 (PVP K
30), poloxamer 407 (POL), polyethylene glycol (PEG), gelucire etc.] can be applied to increase
dissolution rate. hence the solubility of the drug is low at physiological pH. Thus, it is important
to enhance the solubility and dissolution rate of bicalutamide to improve its oral bioavailability. 4

METHODOLOGY:
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 There are two major methods of preparing solid dispersions; melting method and
solvent evaporation method.5

Melting method:
This method consists of melting the drug within the carrier followed by cooling and
pulverization of the obtained product. The process has got some limitations like, use of high
temperature and chance of degradation of drug during melting. 6

Solvent evaporation method:

Solvent evaporation method is a simple way to produce solid dispersions where the drug and
carrier is solubilized in a volatile solvent. The solvent is later evaporated. Tachibani and
Nakumara (1965) were the first to dissolve both the drug and the carrier in a common solvent
and then evaporate the solvent under vacuum to produce a solid mixture. 7
In second generation solid dispersions drugs are molecularly dispersed in an irregular
form within an amorphous carrier which isus ually polymers. 8 The most common solid
dispersions do not use crystalline carriers but amorphous one. According to molecular
interaction of drug and carriers amorphous solid dispersions can be of three types; solid
solutions (van Drooge et al., 2006a; Leuner and Dressman 2000; Van den Mooter et al., 2006),
solid suspensions (van Drooge et al., 2006a; Chiou and Riegelman, 1971; Goldberg et al., 1966b)
or a mixture of both (van Drooge et al., 2006a; van Drooge et al., 2006b). Second generation
solid dispersions use fully synthetic polymers and natural product based polymers as carriers .
Carriers includes polyvinyl pyrrolidone (povidone), poly ethylene glycol, poly methacrylates as a
synthetic and hydroxypropyl methyl cellulose, ethyl cellulose, cyclodextrins as natural product
based polymers.9

ADVANTAGES OF SOLID DISPERSIONS:

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 Vasconcelos et al. (2007) identified four advantageous features of producing solid
dispersions. The features are summarized below:
1. Preparation of solid dispersions results in particles with reduced particle size and thus
the surface area is improved and increased dissolution rate is attained. The ultimate result is
improved bioavailability.
2. Wettability is improved during solid dispersion production. Improved wettability
results in increased solubility. Here the carriers play the major role to improve the wettability of
the particles.
3. Particles in solid dispersions have been found to have a higher degree of porosity. The
increased porosity of solid dispersion particles accelerates the drug release profile. Increased
porosity also depends on the carrier properties.
4. In solid dispersions drugs are presented as supersaturated solutions which are
considered to be metastable polymorphic form. Thus presenting drugs in amorphous form
increase the solubility of the particles .10

NEED OF STUDY:
As stated that the bicalutamide is poorly soluble at normal body condition (5 μg/mL), it
is necessary to increase its bioavailability by using suitable but still economical process. Solid
dispersion method is used for the enhancement in bioavailability.

AIM AND OBJECTIVE:

 The aim of the present study is to enhance the bioavailability of Bicalutamide by using
solid dispersion method.
 To enhance bioavailability by using carriers like HPMC, ethyl cellulose.
 To formulate the bicalutamide tablet.
 To evaluate the bicalutamide tablet.

PLAN OF WORK:

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  Selection of drug and polymers.
 Preformulation study of drug:
 Organoleptic properties
 Solubility
 IR spectroscopy
 UV spectroscopy
 Water content
 Assay
 Preparation of solid dispersion
 Dissolution study of solid dispersion prepared
 Precompression study of solid dispersion
 Angle of repose
 Bulk density
 Carr’s compressibility index
 Hausner’s ratio
 Formulation of compressed tablet
 Evaluation of compressed tablet
 Thickness
 Weight variation test
 Hardness testing
 Friability testing
 Disintegration testing
 Dissolution studies
 Stability testing

MATERIALS:

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  Bicalutamide
 Sodium lauryl sulphate (SLS)
 Hydroxy propyl methyl cellulose (HPMC)
 Iso propyl Alcohol
 Avicel pH101
 Cross povidone
 Lactose
 Aerosil
 Mannitol
 Magnesium stearate
 Talc, Starch

INSTRUMENTS USED:

 Mechanical stirrer
 Rotatory mixer
 Electronic weighing balance
 Digital pH meter
 Tapped density tester
 Multipunch tablet compression machine
 Vernier caliper
 Tablet hardness tester.

 Friability tester

 Disintergration test apparatus

 Dissolution test apparatus.

 Double beam UV – Visible Spectrophotometer

 IR spectrophotometer

REVIEW OF LITERATURE:

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Fuzheng Ren et al. (2006) Characteristics of Bicalutamide Solid Dispersions and improvement
of the Dissolution. They studied the dissolution rate of the physical mixture and solid dispersion
of bicalutamide and PVPK 30 in the solvent absolute alcohol. The resulting mixtures evaluated
by dissolution testing, powder X-ray diffraction, DSC and FT-IR.11
Saha et al. (2002) Enhanced the solubility and dissolution rate of nimesulide and ibuprofen by
solid dispersion techniques and complexation using various hydrophilic excipients. Drug
excipients solid dispersions and complexes of nimesulide were prepared by solvent evaporation
method. Solid dispersion of ibuprofen was prepared by fusion, solvent evaporation, fusion-
solvent method. Solid dispersion of nimesulide with PEG-6000 enhanced the solubility of
nimesulide by more than 1000%. Dispersion of ibuprofen in sorbitol showed maximum
enhancement of solubility (upto 75%). Dispersion in combined carriers: PVP K-30- MCC and PVP
K-30-PEG-6000 also markedly increased the solubility of ibuprofen. Inclusion complexes of
nimesulide in G-cyclodextrin also increased the solubility by 663%. Dissolution rates were
further studied.12
Madhusudhan et al. (2002) Enhanced the solubility of several poorly water-soluble drugs. Solid
dispersion of various compositions were prepared using mannitol as carrier. An improvement in
the solubility and dissolution rates of sulphamethaxozole from solid dispersions was observed. 13
Sapkal et al. (2007) The solid inclusion complexes of gliclazide and β-cyclodextrin were
prepared at a molar ratio of 1:1 and 1:2 by mixing, kneading, and coprecipitation methods both
on small and large scales. The effect of parameters such as kneading time and temperature on
complexation was also studied. Characterization was performed using infrared spectroscopy, X-
ray diffractometry, and dissolution studies. In vitro release studies were carried out in
phosphate buffer (pH 6.8).14
Mooter et al. (2002) Illustrated the mechanism of increased dissolution of diazepam and
temazepam from polyethylene glycol 6000 solid dispersions and concluded that mechanism
involved is solubilization.15
Srikanth M. et al. (2010) Illustreted that the solubility of bicalutamide drug is enhanced by
using complextation process using cyclodextrin by following different techniques like spray
drying, solvent evaporation and kneading method.16

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Chan Li et. Al. (2011) Formulated nanoodispersion of the bicalutamide to enhance the
solubility. Various excipients were selected for the formulation of nanodispersions including
lactose, HPMC, AG and MCC, which was dissolved in water.17
Srikanth M. et al. (2010) Uses adsorption process to improve solubility of bicalutamide. For this
purpose they used the magnesium aluminium silicate, povidone and lactose with the
bicalutamide.18

REFERENCES:

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 1. Srikanth, M. et al. 2010. “Dissolution Rate Enhancement Of Poorly Soluble Bicalutamide
Using Βcyclodextrin Inclusion Complexation.” International Journal of Pharmacy and
Pharmaceutical Sciences Vol 2, Issue 1, 2010: 191-198.
2. Ke, Wu. et al. 2009. “Formation and Characterization of Solid Dispersions of Piroxicam
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7. Tachibana, T. et al. 1965. “A method for preparing an aqueous colloidal dispersion of
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Review.” Journal of Applied Pharmaceutical Science 01 (07); 2011: 13-20.

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 11. Fuzheng, Ren. et al. 2006. “Characteristics of Bicalutamide Solid Dispersions and
improvement of the Dissolution.” Drug Development and Industrial Pharmacy, 32:967–
972, 2006.
12. Saha, R. et al. 2002. “Solubility enhancement of nimesulide and ibuprofen by solid
dispersion technique.” Indian Journal of Pharmaceutical Science. 64:529-534.
13. Madhusudhan, B. 2002. “Studies on sulphamethoxazole solid dispersion and their
tablets.” Indian Journal of Pharmaceutical Science, 64: 233-238.
14. Sapkal, N. 2007. “Evaluation of some Methods for Preparing Gliclazide-β-Cyclodextrin
Inclusion Complexes.” Tropical Journal of Pharmaceutical Research, December 2007; 6
(4): 833-840.
15. Vanden, Mooter. 2002. “ Mechanism of increased dissolution of diazepam and
temazepam from polyethylene glycol 6000 solid dispersions, International Jounal
Pharmaceutics, 249: 45-58.
16. Srikanth, M. et al. 2010. “Dissolution Rate Enhancement Of Poorly Soluble Bicalutamide
Using Βcyclodextrin Inclusion Complexation.” International Journal of Pharmacy and
Pharmaceutical Sciences Vol 2, Issue 1, 2010: 191-198.
17. Chan, Li. et al. 2011. “Formation of bicalutamide nanodispersion for dissolution rate
enhancement.” International Journal of Pharmaceutics 404 (2011) 257–263.
18. Srikanth, M. et al. 2010. “Dissolution Rate Enhancement of Poorly Water Soluble
Bicalutamide by Using Adsorption Process.” International Journal of Pharmaceutical
Research, Volume 2, Issue 4, 2010: 62-66.

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