BIOAVAILABILITY ENHANCEMENT OF A LOW

SOLUBILITY ANTIHYPERTENSIVE DRUG

A

Thesis Submitted to

SVKM’s NMIMS

For the award of the degree of

DOCTOR OF PHILOSOPHY

In

Pharmaceutical Sciences

By

SHILPA P. BHILEGAONKAR

Under the guidance of

PROF. R. S. GAUD

School of Pharmacy & Technology Management,

SVKM’s NMIMS,

Vile Parle (W), Mumbai-400056

2011

ACKNOWLEDGEMENTS First of all I bow to almighty god, by the grace of whom, the project undertaken has reached its

successful completion.

During the progress of this research work, I came across various situations, when I needed help from

someone. Apart from my supervisor, colleagues , family and friends, there are various comparatively

strangers who helped me at time of need because of their sheer goodness of heart. Although I cannot

repay the help and guidance that I have received, I just want to pen down few words of gratitude.

It is my great privilege to express my gratitude to Prof. R.S.Gaud, Dean, School of Pharmacy and

Technology Management (SPTM) Mumbai for his supervision, advice and guidance for every stage of this

research as well as his encouragement and support at time of need.This thesis would not have been

possible without the inspiration and motivation of my supervisor. It has been said that the main thing

about getting ahead is getting started and this project could not have started without contribution of

him.My regards for him are beyond expression of words.

I am grateful to Dr. (Mrs.) Bala Prabhakar, Associate Dean, HOD of Pharmaceutics, SPTM, for her timely

help and motivation during the project work.

I am thankful to Ms. Sangeeta Chavada, Alembic Ltd, Vadodara, for providing gift sample of candesartan

cilexetil needed for this project.

I sincerely thank Prof. Pradeep Vavia, UICT, Mumbai for his guidance on cyclodextrin complexation.

A very special word of thank to Mr. Ashok Omary,Vice President, US Vitamins Ltd, Mumbai for providing

gift sample of candesartan required for In vivo testing of samples and for providing freeze drying facility.

It is indeed a great pleasure to acknowledge the spontaneous cooperation of Dr. Mamata

Mukhopadhyay, Prof. Sandip Roy and Mr. Yogesh Kadam, IIT, Mumbai for permitting me to use their

Supercritical fluid facility.

I am thankful to Mr.C.M. Kulkarni ,Tritech instruments,Mumbai and Mr.Umesh Taralkar for providing

me facility for particle size analysis.

I offer sincere appreciation to Dr. Shashi Menon,TDM laboratories,Mumbai, for his help in carrying out

LC-MS/MS analysis of plasma samples.

I also like to acknowledge and thank Dr.Nancy Pandita, Dr.Ganga Srinivasan, Dr.Meena Chintamaneni,

Dr.Vaishali Londhe, all faculties and staff of SPTM, Mumbai for their help and motivation during the

course of project.

A special thanks to my juniors Divyen and Swarnali for their timely help during project work.

I am blessed to have friends like Reema, Pravin, Amit, Anand, Deepali and Geeta who selflessly stood by

me all the times during my practical work.

I thank SPTM,Mumbai,for providing me facilities required for this project.

No words are enough to express the support what I received from my husband Mr.Prasad Bhilegaonkar

and son Amogh. They have been encouraging and never away from me, when I needed them most. I am

highly grateful to god to have been gifted with a wonderful family.

I extend my sincere thanks to my mother- in- law Ms.Rajani Bhilegaonkar, my father Mr.Shamrao

Kulkarni,my mother Mrs.Shamala Kulkarni and all my family members for their never-ending support and

care during my project work.

I thank to all those who by mistake are remained to name here.

Finally ,but all above,I have no words to express my thankfulness to almighty god for his blessings with

which,I not only able to complete task,but also was taught with new experiences.

Date-21 st February 2010 Mrs.Shilpa P.Bhilegaonkar

This project is dedicated to

My Beloved Family and Respected Guide

Without whom this work wouldn’t have reached its conclusion

i

Statement by the candidate

This is to submit that this written submission in my thesis entitled “Bioavailability

enhancement of a low solubility antihypertensive drug” represents my

ideas in my own words and where others’ ideas or words have been included,

I have adequately cited and referenced the original sources. I also declare that I have

stick to all principles of academic honesty and integrity and have not misrepresented

or fabricated or falsified any idea / data / fact / source in my submission. I

understand that any violation of the above will be cause for disciplinary action by the

School and can also evoke penal action from the sources which have thus not been

properly cited or from whom proper permission has not been taken when needed.

Mrs. Shilpa P. Bhilegaonkar

Forwarded Through

Guide

Prof. R. S.Gaud

Dean

School of Pharmacy & Technology Management,

SVKM’s NMIMS,

Vile Parle (W),

Mumbai – 400056

ii

Certificate

The work described in this thesis entitled “Bioavailability enhancement of a low

solubility antihypertensive drug” has been carried out by Mrs. Shilpa Prasad

Bhilegaonkar under my supervision. I certify that this is her bonafide work. The work

described is original and has not been submitted for any degree to this or any other

university.

Date: Guide

Place: Mumbai Prof. R. S. Gaud

Dean, SPTM, NMIMS

______________________ ______________________

Dr.Bala Prabhakar Prof. R.S.Gaud

Head, Dean, SPTM, NMIMS

Department of Pharmaceutics

SPTM, NMIMS

School of Pharmacy & Technology Management,

SVKM’s NMIMS,

Vile Parle (W), Mumbai-400056

iii

Approval Sheet

(To be completed at the time of final presentation and viva voce)

This thesis entitled “Bioavailability enhancement of a low solubility

antihypertensive drug” by Mrs.Shilpa Prasad Bhilegaonkar is approved for the

degree of Doctor of philosophy in pharmaceutical Sciences.

Examiners

________________________

________________________

_______________________

Supervisor (s)

________________________

______________________

________________________

Chairman

________________________

Date :____________

Place :____________