Journal of Applied Solution Chemistry and Modeling, 2013, 2, 145-157 145
E-ISSN: 1929-5030/13 © 2013 Lifescience Global
Improvement of Dissolution Rate of Chlorzoxazone by Solid
Dispersion Technique and Development of Buccal Patch
Swati Jagdale
*
, Asawaree Hable, Aniruddha Chabukswar and Bhanudas Kuchekar
MAEER’s Maharashtra Institute of Pharmacy, S. No. 124, MIT Campus, Paud Road, Kothrud, Pune-411038,
India
Abstract: Chlorzoxazone (CLZ) is insoluble in water. Its half life is 1.1 hr, dose is 250 mg and has first pass metabolism.
Formation of solid dispersions of CLZ with pluronic F127 will enhance the bioavailability of the drug. Phase-solubility
studies revealed AL type of curves, indicating the ability of pluronic F127 to disperse with CLZ and significantly increase
in solubility. The solid dispersions of CLZ was carried out with pluronic F127 by different methods and characterized by
in vitro drug release, drug content, FTIR, DSC, XRD. All the solid dispersions showed dissolution improvement compare
to pure drug. These techniques revealed distinct loss of drug crystallinity in the formulation accounting for enhancement
in dissolution rate. The stability study for solid dispersions indicated, all formulations were stable. Methods showing best
in vitro drug release profile were selected in further development of mucoadhesive buccal patches. A buccal patch has
been developed using mucoadhesive polymers HPMC K4M and carbapol 974. The developed patches were evaluated
for the physicochemical, mechanical and drug release characteristics. The optimized patches showed good mechanical
and physicochemical properties to withstand environment of oral cavity. The in-vitro permeation study showed that
patches could deliver drug to the oral mucosa for a period of 8 hrs. The results indicate that suitable bioadhesive buccal
patches with good permeability could be prepared. The batches FH4 and FC4 showed 79.65% and 79.93% permeated
through goat mucosa membrane in 8 hrs. The stability study for buccal patch revealed that all batches were stable.
Keywords: Solid dispersions, pluronic F127, chlorzoxazone, dissolution studies, buccal patch.
1. INTRODUCTION
The poor solubility of drug (BCS Class II) in
gastrointestinal fluid gives rise to variations in
dissolution rate and incomplete bioavailability. An
improvement of the dissolution rates of water-insoluble
drugs is one of the most challenging and important
tasks of drug development as it can increase drug
bioavailability [1-3]. Chemically, Chlorzoxazone (CLZ)
is 5-chloro-3H-benzooxazol-2-one, which belongs to
skeletal muscle relaxant (centrally acting) class. It has
half life of 1.1 hours & dose is 250mg. It is soluble in
methanol, ethanol & isopropanol; freely soluble in aq.
solutions of alkali hydroxides and slightly soluble in
water. It is necessary to improve the dissolution rate of
CLZ to enhance the bioavailability [4-5].
There are different chemical or formulation
approaches to improve drug dissolution and
bioavailability. Among the various strategies solid
dispersion technique has often proved to be the most
successful in improving the dissolution and
bioavailability of poorly soluble drug. There are different
methods for preparation of solid dispersion. Solid
dispersion is most successful technique as it is simple,
economic, and advantageous to enhance dissolution
rate [6-13].
*Address correspondence to this author at the Department of Pharmaceutics,
MAAER’s Maharashtra Institute of Pharmacy, S. No. 124, MIT Campus, Ex-
serviceman Colony, Paud Road, Kothrud, Pune-411038, India; Tel: +91-
9881478118; E-mail: jagdaleswati@rediffmail.com
Buccal delivery of drugs provides an attractive
alternate to the oral route of drug administration,
particularly in overcoming deficiencies associated with
the latter mode of dosing. Problems such as high first
pass metabolism and drug degradation in
gastrointestinal environment can be circumvented by
administering the drug via the buccal route. It is also
possible to administer drugs to patients who cannot be
dosed orally. Therefore, adhesive mucosal dosage
forms were suggested for oral delivery that included
adhesive tablets adhesive gels and adhesive patches.
However, buccal patches are preferable over adhesive
tablets in terms of flexibility and comfort. Now day’s
bioadhesive polymers received considerable attention
as platforms for buccal controlled delivery due to their
ability to localize the dosage form in specific regions to
enhance drug bioavailability. In order to prepare films
having the appropriate characteristics, film-forming
polymers were initially used alone and successively in
combination with mucoadhesive polymers. The patches
with the best characteristics were selected for testing.
The plasticizer interposes itself between the polymer
chains and interacts with the forces held together by
extending and softening the polymer matrix. The
commonly used plasticizers include phthalate esters,
phosphate esters, fatty acid esters and glycol
derivatives [14-19].
The solid dispersion showing best in vitro drug
release profile can be selected in further development
of buccal patches of CLZ. This would help to facilitate