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ABSTRACT
The aim of present investigation was to compare the ionotropic gelation techniques for entrapping water soluble drug Diltiazem HCl in mucoadhesive
microparticulate system. Mucoadhesive polymers HPMC K15 and Carbapol 934 were used in combination with sodium alginate which provides gastric
retention for prolonged time. Diltiazem HCl microcapsules were formulated by orifice-ionic and emulsification-ionic gelation technique. The formulated microcapsules
of Diltiazem HCl were evaluated for the following parameters viz. Particle size, entrapment efficiency, in-vitro drug release and percent mucoadhesive strength.
FT-IR and SEM were used to characterize microcapsules. The results of both techniques were compared. It was evident from study that, the entrapment
efficiency of Diltiazem HCl was improved (46% - 61%) in emulsification-ionic gelation technique, as compared to orifice-ionic gelation technique (<15%). Thus
it was concluded that emulsification-ionic gelation technique is superior to orifice-ionic gelation technique to entrap water soluble drug Diltiazem HCl. The drug
release from the microcapsules were found to be slow and spread over extended period of time, drug release depends on the percent of coat material, wall thickness
and size of microcapsule. Microcapsule with a coat comprised sodium alginate, HPMC and carbapol exhibited good mucoadhesive properties as observed in in-
vitro wash-off test.
INTRODUCTION
Oral bioavailability of certain drug can be limited by the residence India). Sodium alginate was gift sample from TIC Gums (USA), HPMC K15
time of the pharmaceutical formulations in the upper gastrointestinal tract. (Colorcon Asia PVT, LTD. Goa India), Carbapol (Noveon USA) and all other
Gastric emptying plays an important role in the dynamics of drug absorption chemicals used were of analytical grade.
and can lead to variable and unpredictable availability. The ability to maintain an
oral delivery system at the target absorption location for an extended period of METHODS:
time has great appeal for treatment of both local conditions as well as for
sustained systemic absorption. Several strategies have been proposed to modify preparation of mucoadhesive microcapsule of diltiazem hcl by
the GI transit of oral pharmaceutical formulations such as floating, high-density orifice- ionic gelation method
system, expandable, swelling system etc. Mucoadhesive drug delivery is one of
the approaches to design a formulation, which can adhere to the lining of the Microcapsules were prepared by orifice-ionic gelation method. So-
stomach, thus retaining the drug at the target absorption site for a prolonged dium alginate and mucoadhesive polymer such as HPMC K15 and Carbopol
period. This approach involves the use of bioadhesive polymers, which can 934 were dissolved in purified water to form a homogeneous polymer solution.
adhere to the epithelial surface in the stomach [1, 2]. The core material as fine powder was passed through mesh no. 120, added to
the polymer solution and mixed to form a smooth viscous dispersion. This
Drug delivery systems (DDS) that can precisely control the release dispersion was added drop wise into 10%w/v CaCl2 solution through a syringe
rates or target drugs to a specific body site had an enormous impact on the with a needle of diameter 0.55mm. The added droplets were retained in CaCl2
healthcare system. Carrier technology offers an intelligent approach for drug solution and allowed to cure for 20 minutes at 200 rpm to produce spherical
delivery by coupling the drug to a carrier particle such as microspheres, rigid microcapsules. The microcapsules were collected and dried in an oven at a
nanoparticles, liposomes, etc. which modulates the release and absorption char- temperature 450 C for 12 h.
acteristics of the drug. Bioadhesive microspheres include microparticles and
microcapsules (having a core of the drug) of 1–1000µm in diameter and consist- preparation of mucoadhesive microcapsule of diltiazem hcl by emulsifi-
ing either entirely of a bioadhesive polymer or having an outer coating of it, cation ionic gelation method. [4,5,6].
respectively. Microparticles constitute an important part of these particulate
DDS by virtue of their small size and efficient carrier characteristics. However, The microcapsules were formulated as per the same formulation
the success of these novel DDS is limited due to their short residence time at the compositions as described in the previous method. The dispersion of drug and
site of absorption. It would, therefore, be advantageous to have means for polymer with sodium alginate was added dropwise into 300 ml of olive oil
providing an intimate contact of the DDS with the absorbing membranes. It can containing 1.5% span with stirring at 200 rpm. Stirring was continued for 5 min
be achieved by coupling bioadhesion characteristics to microparticle and devel- to emulsify droplets. The droplets were cured for 20 min in calcium chloride
oping novel delivery systems referred to as “bioadhesive microparticle” [1,3]. (10% w/v) solution. Finally, the microcapsules were filtered, washed and dried
at 45ºC for 12 h.
MATERIALS:
Diltiazem HCl was a generous gift sample from ZIM Labs (Nagpur, Comparative evaluation of formulated microcapsules
% cumulative drug
80 MH1
DIL I
% Entrapment efficiency
100
DIL II MH2
60 80
release
MH3
60 MC1
40
40 MC2
20 20 MC3
0
0 0 2 4 6 8 10
MH1 MH2 MH3 MC1 MC2 MC3 Time (hrs)
Batch Code Fig 4: Cumulative % drug release of diltiazem HCl in pH 6.8
Figure 1: Comparative entrapment efficiency of dltiazem HCl 120
% Mucoadhesion
microcapsules prepared by orifice-ionic and emulsification ionic gela- 100
tion method. 80 MH1
60 MH2
40 MH3
20 MC1
0
MC2
0 2 4 6 8 10
MC3
Time (hr)
100
MH1
80
MH2
60 MH3
40 MC1
MC2
20
MC3
0
0 1 2 3 4 5 6 7
Time (hr)
c)Spherical microcapsule with size 851.2 (×85) d) surface texture of Fig 6: Mucoadhesion behaviour of microcapsule formulations in 6.8
microcapsules(×1500) Diltiazem HCl microcapsules prepared by
buffer
emulsification-ionic gelation method
120 120
% Mucoadhesion
100 100
MH1
% cumulative drug
MH1 80
80 MH2
MH2 60
release
60 MH3 40 MH3
MC1 MC1
20
40 MC2
MC3 0 MC2
20 0 2 4 6 8 10 MC3
0 Time (hrs)
0 2 4 6 Time 8 10 12 14
Figure 2: Scanning electron microscopy of Diltiazem HCl microcapsules Fig 7: Mucoadhesion behaviour of microcapsule formulations in pH 1.2
prepared by ionic gelation method 120
120 100
% Mucoadhesion
% cumulative drug
MH1
100 80
MH2 MH1
80 60
release
MH3 MH2
60 MC1 40 MH3
MC1
40 MC2 20
MC2
0
20 MC3 MC3
0 2 4 6 8 10
0
Time (hrs)
0 2 4 6 8 10
Time (hrs)
Fig 8: Mucoadhesion behaviour of microcapsule formulations in pH 6.8
Fig 3: Cumulative % drug release of diltiazem HCl in pH 1.2
Journal of Pharmacy Research Vol.3.Issue 7.July 2010 1531-1534
Tirupati M. Rasala et al. / Journal of Pharmacy Research 2010, 3(7),1531-1534
indicates that it follows non-fickian diffusion. The formulation batch MC3 ACKNOWLEDGMENTS:
follows the zero order release which show constant drug release rate with time
(table 4). The authors are very much thankful to ZIM Lab, Colorcon, Noveon,
TIC gums for providing gift sample and also to UGC for providing financial
CONCLUSION: assistance.