INTRODUCTION : Drug delivery system can be defined as the mechanisms to set up
therapeutic agents into the body. Primitive approaches of delivering drugs lacked a
very basic need in drug delivery; that is, consistency and uniformity which are safe,
economical and efficient for means of providing the health and wellbeing of
mankind. An perfect dosage regimen in the drug therapy of any disease is the one
that instantly attains the preferred therapeutic concentration of drug in plasma and
maintains it steady for the entire duration of treatment. This is possible through
administration of a conventional dosage form in a particular dose and at a particular
frequency resulting in a number of limitations. To overcome those limitations
effective and safer use of existing drugs through concepts and techniques of
modified release and targeted delivery system can result in increased interest.
AIM AND OBJECTIVE :
The aim and need of this study was directed to develop, optimize and
evaluate an efficient CTDDS in two parts. First part deals with budesonide burst
release Crospovidone and pH dependent Eudragit L30D coated tablets for ileo
caecal targeting to treat mild to moderate CD and in second part budesonide
sustained release HPMC K4M and Eudragit L30D coated tablets developed for
colonic delivery to treat mild to moderate IBD and for maintenance therapy during
disease remission.
Budesonide were selected as model standard drugs to treat IBD.
Budesonide is a potent, synthetic non-halogenated corticosteroid with high topical
anti-inflammatory effect and little systemic effects. Additionally, budesonide has
low incidence of adverse effects and high topical effects and has important
suggestions in the pharmacotherapy of IBD, both in treatment of UC and CD. It was
found that less than 5% of drug was available beyond the ileum and cecum, and
hence, colonic delivery still needs to be optimized by a more reliable targeted
system.
In the present research it was therefore decided to determine whether better
formulations for colonic delivery could be formulated as coated with pH sensitive
polymer with burst release of budesonide and sustained release budesonide tablets
has advantages of bioavailability of high drug concentration at targeted site,
reduction in dosage regimen and moreover controlling drug release respectively.
The following objectives were outlined to achieve the aim and need of the
study:
1. To select appropriate drug and polymers to formulate two colonic
delivery systems to treat CD and IBD i.e. a burst immediate release
and a sustained release system, both coated with pH dependant
solubility profiles to achieve lag time of 5h respectively,
2. To perform Preformulation studies,
3. To develop budesonide loaded tablets with Crospovidone and based
on coating with Eudragit L30D,
4. To develop a budesonide loaded tablets with HPMC K4M and based
on coating with Eudragit L30D,
5. To perform in vitro release studies & other evaluation parameters for
both formulations,
6. Optimization of both formulations,
7. Stability study of both optimized formulations,
8. To perform in vivo animal studies to perform site specificity by Xray
imaging and establish pharmacokinetic parameters.
MATERIALS AND METHODS :
Budesonide was a kind gift from Ethypharma Pvt. Ltd. (Mumbai, India).
Eudragit L30D was purchased from the Research-Lab Fine Chem Industries
(Mumbai, India). Polyethylene Glycol was purchased from Clariant Pvt. Ltd.
(Mumbai, India). Magnesium Stearate, lactose, polyvinyl pyrolidone (PVP K30),
Methylene chloride were purchased from Signet India Pvt. Ltd, Mumbai. HPMC
K4M, Crospovidone and Isopropyl alcohol (IPA) were purchased from Loba
Chemicals (Mumbai, India). Other excipients used were of standard pharmaceutical
Grade. Compatibility study of budesonide pure drug, excipients and its physical
mixture was evaluated. Melting point of drug was determined using melting point
apparatus using capillary method. The calibration curves of budesonide were
measured in distilled water, 0.1N HCl and phosphate buffers of 6.8 and 7.4 pH.
Compatibility study of budesonide pure drug, excipients and its physical
mixture was evaluated. Solubility determination and melting point of drug was
determined using melting point apparatus using capillary method. The reported
analytical method in methanol was tried by using UV spectrophotometer.
RESULT : Compatibility study of budesonide pure drug, excipients and its physical
mixture was evaluated and passed as per standards. The melting point of budesonide
was determined by using capillary method and was found to be 241-245°C
(Standard 245-255°C) which complies with the reported value. The calibration
curves of budesonide were measured in distilled water, 0.1N HCl and phosphate
buffers of 6.8 and 7.4 pH which showed good linearity with the regression
coefficient (R2) as 0.997, 0.998, 0.999 and 0.999 respectively. Budesonide was
loaded with Crospovidone and tablets were effectively coated with successive layers
of Eudragit L30D on preliminary trial basis. The process had an efficiency of ~90%
and ~90–95% in polymeric coating. Compatibility study of budesonide pure drug, excipients and its physical mixture was evaluated and passed as per standards. The melting point of budesonide
was determined by using capillary method and was found to be 241-245°C
(Standard 245-255°C) which complies with the reported value. CONCLUSION :
From the present study it was concluded that, the budesonide pH
dependant burst release might be successful preference for ileo-cecal targeting by
achieving the desired lag time to treat CD effectively. Also budesonide pH
dependant sustain released optimized formulation could be best choice for colon
targeted drug delivery by achieving the desired lag time. Satisfactory results were
found from evaluation of micromeritic parameters such as flow property, in vitro
dissolution study and kinetic study
