FORMULATION AND EVALUATION OF SOLID DISPERSION FOR

ANTI HYPERTENSIVE DRUG

M.PHARM DISSERTATION PROTOCOL

SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA
BY
P.D CHAITHANYA
I M.PHARM
UNDER THE GUIDENCE OF

DR. B. PRAKASH RAO M. Pharm, Ph. D.

PROFESSOR, HEAD OF THE DEPARTMENT

DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY

KARNATAKA COLLEGE OF PHARMACY

DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY

KARNATAKA COLLEGE OF PHARMACY
BANGALORE-560064
2012-2014

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 RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA

ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1 Name of the Candidate and Address P. D. CHAITHANYA

Karnataka College of Pharmacy
#33/2, Thirumena Halli
Hegde Nagar Main Road
Bangalore-560064.
PERMANENT ADDRES
D.NO;-19-8-18F,
DASARIMATAM,
TIRUPATHI.
517501

2 Name of the Institute Karnataka College of Pharmacy

#33/2, Thirumena Halli
Hegde Nagar Main Road
Bangalore-560064.

3 Course of the Study & Subject Master in Pharmacy

( Pharmaceutical technology)

08-01-2013
4 Date of Admission to the Course

5 Title of Topic
FORMULATION AND EVALUATION OF SOLID DISPERSION FOR

ANTI HYPERTENSIVE DRUG

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6.1 Need of Study

Oral drug delivery is the most popular, simplest and easiest way of
administering drugs. Because of the greater stability, smaller bulk, accurate dosage
and easy production, solid oral dosages forms have many advantages over other types
of oral dosage forms1

The term solid dispersion defined as the dispersion of one or more active
ingredient in an inert carrier or matrix at solid state prepared by melting (fusion),
solvent, or the melting solvent method. Sekiguchi et.al. Suggested that the drug was
present in a eutectic mixture in a microcrystalline state2

Solid dispersions are one of the most successful strategies to improve

drug release of poorly water-soluble drugs. The solid dispersion refers to a group of
solid products consisting of at least two different components, generally a hydrophilic
matrix and a hydrophobic drug. Several hydrophilic carriers like Polyethylene glycol
(PEGs), Polyvinyl Pyrrolidone (PVP), Hydroxypropyl cellulose (HPC), β-Cylodextrin
etc have been investigated as inert matrices for enhancing solubility and dissolution
rate.

The approaches that have commonly been used to overcome drawbacks

associated with poorly watersoluble drugs, in general includes micronization, salt
formation, use of surfactant and use of pro- drug

The formulation of drugs having low aqueous solubility using solid dispersion
technology has been an active area of research since 1960

The Anti-Hypertensive Drugs which belongs to BCS class-II having low

aqueous solubility and high membrane permeability. The bioavailability of Anti-
Hypertensive drugs have low to elicit the required pharmacological effect, hence
making it a suitable candidate for the proposed research work with an aim of
improving its oral bioavailability.

SReview of Literature
It stated that improved its dissolution of solid dispersions of Ibuprofen were
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 prepared using polyethylene glycol 20000 in a relatively easy and simple manner,
6.2 characterized by scanning electron microscopy (SEM), differential scanning
calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), and evaluated
for solubility and in vitro drug release.3

Solid dispersions of poorly water soluble drug Irbesartan in hydrophilic

carrier matrix have been reported as the better method to improve theirsolubility and
dissolution rate.4

Solid dispersions of Anti-Hypertensive drug Felodipine were prepared by

using poly acrylic acid as polymer. Samples were prepared with different drug loading
and analyzed using differential scanning calorimetry (DSC). The solid dispersions of
Felodipine with poly acrylic acid showed enhanced dissolution when compared to pure
Felodipine.5

Solid dispersions of Nifedipine and Carbamazepine were prepared by a

melting method from the water-insoluble model drugs carbamazepine and nifedipine
and polyethylene glycol 1500 or 1:1 mixtures of PEG 1500 and the polymers
polyvinylpyrrolidone (PVP 30, PVP 12), polyvinylpyrrolidone-co-vinylacetate
(PVPVA) and Eudragit.6

The effect of polyethylene glycol 4000 (PEG 4000) on invitro dissolution

of gliclazide from solid dispersions. Solid dispersions were prepared by the melting or
fusion method. In conclusion, dissolution of gliclazide can be enhanced by the use of
hydrophilic carrier.7

The influence of polyethylene glycol 4000 (PEG) and

polyvinylpyrrolidone K30 (PVP) on in vitro dissolution of etoricoxib from solid
dispersions. Solid dispersions were prepared using the solvent evaporation method.
PEG was found to be more effective in increasing the drug dissolution compared to
PVP.8

The prepared solid dispersions of Simvastatin with inert carriers in an

attempt to improve the release profile. Simvastatin solid dispersions with polyethylene
glycol (PEG 6000) or poly vinyl pyrrolidone (PVP K15) in 1:1, 1:2, 1: 3, 1:4, and 1:5
ratios were prepared by melting method, solvent evaporation method and melting

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 solvent method. Drug release from all solid dispersions was significantly improved
when compared to their corresponding physical mixture or drug alone. The
preparation of Simvastatin SD with PEG or PVP is a promising strategy to improve
the bioavailability of the drug.9

Solid dispersions of Prednisone which were prepared by the solvent

evaporation method at different drug: polymer ratios (wt/wt). The physical state and
drug: carrier interactions were analyzed by X-ray diffraction, infrared spectroscopy, and
scanning electron microscopy. The dissolution rate of prednisone from solid dispersions
was markedly enhanced by increasing the polymer concentration.10

The prepared solid dispersion by Fourier transform infrared (FTIR)

spectroscopy, powder X-ray diffraction, and thermal analysis techniques. Optimized the
formulation, solid dispersions were prepared employing different methods
usingdifferent carriers with various drugs: carrier ratios. Their dissolution behaviors
were also compared. The results indicated that in vitro dissolution rate of PRD was
remarkably improved in the solid dispersion of the drug compared with physical
mixture and drug alone.11

Evaluate the solid dispersions of Furosemide and the study showed that the
dissolution rate of furosemide enhanced considerably by formulating in it as a solid
dispersion in Sodium starch glycolate using a kneading method. Incorporation of
superdisintegrants in the solid dispersions played a critical role in dissolution
enhancement12.

Evaluate the solid dispersions of Ibuprofen and they were evaluated for
solubility, in vitro release and oral bioavailability of ibuprofen in rats. Quicker release
of ibuprofen from SDs in rat intestine resulted in a significant increase in AUC and
Cmax, and a significant decrease in Tmax over pure ibuprofen. SDs by low temperature
melting method using PEG 6000 as a meltable hydrophilic polymer carrier could be a
promising approach to improve solubility, dissolution, and absorption rate of
ibuprofen.13

The in vitro evaluation of piroxicam solid dispersions containing

hydroxypropyl methylcellulose acetate succinate (HPMCAS-LF, -HF) as a carrier.
Binary (piroxicam–HPMCAS) and ternary (piroxicam–HPMCAS–Carbopol 940) solid
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 dispersions were prepared by spray-drying method. In vitro release was studied using a
flow-through cell technique. Studies of dissolution rate of piroxicam from solid
dispersions were carried out in comparison with corresponding physical mixtures
and drug alone. The dissolution profiles depend on the presence of Carbopol 940 in
solid dispersions.14

The fenofibrate solid dispersions with high bioavailability using

hotmelt extrusion and compare the difference of Eudragit E100 and
polyvinylpyrrolidone-vinyl acetate copolymer S630 (PVP-VA) in dissolution. In vitro
dissolution test and in vivo bioavailability of the drug was studied. Eudragit E100 1:4
solid dispersion has lower dissolution in 0.1M HCl and higher dissolution in water.
Hot-melt extrusion is an excellent method to improve the dissolution and therefore the
bioavailability of fenofibrate.15

The stability studies of Solid dispersions were successfully

performed. Production of amorphous solid dispersions proved to be successful, the
alterations seen in the physical state of itraconazole upon storage affect its dissolution
behaviour. For the 50/50 dispersion, crystallization of itraconazole reduced the
dissolution performance of the powder. For the 40/60 dispersion, some crystallization
could be observed. The 30/70 and 20/80 dispersions showed the absence of
crystallization. For the 40/60, 30/70 and 20/80 dispersions, an increase in dissolution
performance was seen after 10 months of storage. In vivo results in the rat proved the
presented approach to be potentially useful for the formulation of solid dispersions of
itraconazole.16

6.3 Objective of the Study:

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 The objectives of the proposed study are:-

1 Preformulation study of the drug candidates and polymer carriers. (FTIR, DSC)
2 Preparation of solid dispersions of an Anti Hypertensive drug by feasible
(Lyophilizer) method.
3 Characterization of the prepared solid dispersions.
4 Evaluate the prepared solid dispersion for its physico-chemical properties.
5 Studies of the selected solid dispersions.

7 Materials & Methods

Source of Data
7.1
The data will be obtained from

 The literature survey and Internet source.

 Digital Library, R.G.U.H.S, Bangalore.
 Library, Karnataka College of Pharmacy, Bangalore.
 The experimental work, which includes preformulation, formulation and
characterization of solid dispersions by various techniques using suitable drug
candidates.
7.2 Method of Collection of Data

 Data on drug and excipients will be collected from the drug information center,
Reference books, Text books, catalogs etc.
 Data will be collected from the prepared formulations, in-vitro dissolution
studies and stability studies. In-vitro Dissolution studies will be used as criteria
for assessing the enhancement of oral bioavailability of poorly aqueous soluble
drug.

7.3 Materials

 Drug: The Anti Hypertensive drugs will be procured or obtained from suitable
Pharma grade Manufacturer.
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  Polymers: The suitable natural, biodegradable, synthetic polymers and its
derivatives from Pharma grade Manufacturer.
 All other materials and chemicals will be used of Analytical grade

7.4 Method

1. Pre formulation
 Preliminary Morphological Studies.
 Compatibility and Incompatibility Studies.
2. Preparation of solid dispersion
 Melt Method.
 Solvent Evaporation.
 Spray Drying.
 Freeze Drying.
3. Evaluation
 Physico-chemical properties of solid dispersions.
 Release study.
 Comparative study of selected formulation with Marketed Product.
 Stability study as per ICH Guidelines.

7.5 Does the study require any investigations or interventions to be conducted

On patients or other human or animals? If so please describe briefly
NOT APPLICABLE

7.6 Has the Ethical Clearance been obtained from your Institution in case of 7.5?
NO

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8 LIST OF REFERENCES
1. Youn YS, Improved intestinal delivery of salmon calcitonin by Lys18- amine
specific PEGylation: Stability, permeability, pharmacokinetic behavior and in vivo
hypocalcemic efficacy. J. Contr. Release 114,2006, 334–342.
2. Chiou WL, Riegelman S, Pharmaceutical applications of solid dispersion
systems, J. Pharm. Sci, 60, 1971, 1281-1302
3. Madhuri N, Krishna HB, Dong XL, Jung HS, Jung AK, Bong KY et al.
Enhanced dissolution of ibuprofen using solid dispersion with polyethylene glycol
20000. Drug Dev Ind Pharm 2008;34:1013-21.
4. Garima C, Arvind KB. Improved dissolution of a poorly water soluble drug in
solid dispersions with polymeric and non polymeric hydrophilic additives. Acta
Pharm 2008;58:257-74.
5. Dexi L, Yanbin H. A thermal analysis method to predict the complete phase
diagram of drug polymer solid dispersions. Int J Pharm 2010;399:109-15.
6.Heike B, Bernd F, Roland B. Characterization and stability of solid dispersions
based on PEG polymer blends. Int J Pharm 2010;390:165-73.
7.Moreshwar PP, Naresh JG. Preparation and characterization of gliclazide
polyethylene glycol 4000 solid dispersions. Acta Pharm 2009;59:57-65.
8.Bhanubhai NS, Haresh MP, Shailesh AS, Ishwarnish R, Vijay KP. Preparation
and characterization of etoricoxib polyethylene glycol 4000 plus poly vinyl
pyrrolidone K30 solid dispersions. Acta Pharm 2006;56:285-98.
9.Taizia DS, Valquiria TA, Jackson ALCR, Nivaldo LS, Renata BO, Cristina
DVS. Preparation and characterization of solid dispersion of simvastatin. Drug
Dev Ind Pharm 2010;36(11):1348-55.
10.Dario L, Maria GB, Maria CL, Claudio JS. Development of Prednisone
polyethylene glycol 6000 fast release tablets from solid dispersions solid state
characterization dissolution behavior and formulation parameters. AAPS Pharm
Sci Tech 2007;8(4):E1-7.
11.Mohanraj P, Jasmina K. solid dispersion of prednisolone: solid state
characterization and improvement of dissolution profile. Drug Dev Ind Pharm
2010:1-15.

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12.Ganesh C, Piyush P, Sharwaree H, Mukul K, Ashok B, Sagar B. Formulation
and evaluation of solid dispersions of furosemide in sodium starch glycolate.
Trop J Pharm Res 2009 Feb;8(1):43-51.
13. Madhuri N, Krishna HB, Jung Ak, Bong KY, Han GC, Chul SY. Preparation
and evaluation of fast dissolving ibuprofen polyethylene glycol 6000 solid
dispersions. Drug Deliv 2008;15:355-64.
14.Renata J, Anna C. Preparation and evaluation of piroxicam HPMCAS solid
dispersions for ocular use. Pharm Dev Tech 2008;13:495-504.
15.Haibeng H, Rui Y, Xing T. In vitro and in vivo evaluation of fenofibrate solid
dispersion prepared by hot melt extrusion. Drug Dev Ind Pharm 2010;36(6):681-
7.
16.Bernard VE, Michiel VS, Raf M, Kristof H, Johan AM, Ludo F et al.
Itraconazole TPGS aerosil 200 solid dispersions characterization physical stability
and in vivo performance. Eur J Pharm Sci 2009;38:270-8.

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9. Signature of the Candidate (P.D. CHAITHANYA)

10. Remarks of the Guide

The topic selected for dissertation is satisfactory. Adequate equipment &

chemicals are available to carry out the project work.

11. Name & Designation (in BLOCK LETTERS)

11.1 Guide DR.B.PRAKASH RAO

PROFESSOR, HEAD OF THE
DEPARTMENT
PHARMACEUTICAL TECHNOLOGY
KARNATAKA COLLEGE OF
PHARMACY
BANGALORE-560064.

OH

11.2 Signature of Guide I ( DR.B.PRAKASH RAO)

11.3 Co-Guide NOT APPLICABLE

11.4 Signature of Co-Guide NOT APPLICABLE

11.5 Head of the Department DR.B.PRAKASH RAO

HOD OF PHARMACEUTICAL
TECHNOLOGY
KARNATAKA COLLEGE OF
PHARMACY
BANGALORE-560064.

11.6 Signature of HOD ( DR.B.PRAKASH RAO)

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12.

12.1 Remark of the Principal

All the required facilities will be provided to carry out dissertation work under the
supervision of the guide.
( Dr K.RAMESH )

12.2 Principal PRINCIPAL

Karnataka College of Pharmacy

Bangalore-560064

12.3 Signature of principal

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