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70 M Rahman et al USTA, Vol. 15, No. 1 71
Preparation of Ranitidine Sustained Release Pellet
by Extrusion Spheronization method and
measuring the release profile
Mahmudur Rahman*1, Dr.Sukalyan Kumar Kundu 2
A F M Nazmus Sadat 1
1Department of Pharmacy, USTC
2Department of Pharmacy, Jahangirnagar University, Savar, Dhaka.
Abstract : Ranitidine is widely used in the gastric disease. As they are
very much hygroscopic especial precaution should be taken when
preparing a dosage form. Pellet is very popular dosage form of
ranitidine as they easily distribute in the body and give direct action.
Here we have designed a sustained release pellet of ranitidine using
only one excipient. Here we used the most popular extrusion and
spheronization method. The various release profile and absorbance test
of this dosage form give satisfactory result.
Keywords : Mirocrystalline cellulose (MCC), extrusion spheronization
method, pellets.
Introduction :
Pellets are increasingly being used as multiple unit dosage forms. Pellets
possess many pharmacological advantages as they disperse freely in the
gastrointestinal tract, maximize drug absorption, reduce peak plasma
fluctuations and minimize potential side effects without appreciably
lowering the bioavailability [1]. They avoid high local concentrations of
bioactive agents, which may inherently be irritative or anesthetic to
stomach. Additionally they reduce intra and inter subject variability of
plasma profiles by reducing variations in gastric emptying rates and
overall transit times [2].
Extrusion-spheronization is the most commonly used method for pellet
production [3]. Use of suitable excipients can be made to produce pellets
of desirable quality [4]. Different excipients from a variety of sources have
been evaluated for the formation of spherical pellets [5, 6]. Spherical
* For correspondence : Mahmudur Rahman
76 M Rahman et al USTA, Vol. 15, No. 1 73
pellets possess many advantages, including a low surface area to volume
ratio, good flow properties and uniformity in packing [7]. This ideal
shape of pellets makes them excellent substrates for coating as desired
for aesthetic purposes or controlled release of active ingredients.
Microcrystalline cellulose is the most commonly used excipient in
extrusion spheronization. It leads to the formation of round spheres with
desirable characteristics.
During spheronization, the moisture entrapped in the MCC microfibrils
adds plasticity to the extrudates and helps to round the short extrudates
into spherical pellets [8]. MCC may also act as a crystallite gel [9] or as a
sponge [10] to aid the production of pellets by extrusion-spheronization.
However, MCC obtained from different sources varies widely in
properties. There have been many reports on the inherent variability in
physical properties that exist between MCCs of different batches/
manufacturers.
Materials and Methods
Materials
Microcrystalline cellulose was obtained from Gmbh Co Germany. The
process of extrusion and spheronization has been replaced manually by
syringe and needle. Dicalcium Phosphate dehydrate (DPD) solution has
been used as a medium to make the pellet sphere and round shape. DPD
was obtained from E. Merck Ltd. Mumbai, India. All the chemical and
reagents are used were of analytical grade.
Methods
Preparation of Pellets
The ranitidine content of all pellets was kept constant to 5%. Pellets were
prepared according to the formula given in Table 1. Distilled water was
used as the moistening liquid. The amount of water used for moistening
of different Microcrystalline Cellulose grades (E1-E4) was kept constant.
For all the rest batches the amount of water required for moistening was
as per quantities mentioned in Table 1. Fifty grams of the powder mass
was moistened and extruded through an extruder (manually by
injection) and subsequently spheronized on a spheronizer (manually by
syringe needle and DCPD solution as a medium) at a fixed rpm for 2
minutes.
The spheronization time was kept low so as to clearly differentiate the
effect of the excipient or on the pellet properties (particularly on pellet
shape). The wet pellets thus obtained were dried in a tray dryer at 50 O C
for 24 h.
Table 1 : Details of the Various Batches Prepared for
Extrusion-Spheronization
Excipient % of water used for
Granulation (dry basis)
MCC 1 (E1) 80%
MCC2 (E2) 80%
MCC3 (E3) 80%
MCC4 (E4) 80%
Dissolution Studies and Release Profile :
Effect of different Avicel grades: In order to find out the release profile of
pellets we have used gastric fluid. The gastric fluid is made with 14ml
conc HCl and 2gm NaCl with 1 litre of distilled water [11]. About 2 litres
of gastric fluid was made to find the release profile.
The automatic dissolution machine Pharma Test from Germany has been
used to finish the result. Now the pellets are used for dissolution testing.
The dissolution profiles of the pellets prepared with different MCC are
shown in Fig. 2a and 2c. The dissolution profiles of the drug differed
significantly within the MCC (ANOVA, P<0.05) but in all cases the
dissolution could be described by the Higuchi equation [11]. The percent
release vs. time in all the formulations was found to be linear (r2 = 0.98 to
0.999). Thus it is concluded that MCC acted as an inert matrix from
which the drug release occurred via diffusion. The difference in the
release rate from different MCC grades can be attributed to many factors.
According to Alvarez et al., 2002 [12]. MCC with larger particle size has
higher porosity. The average particle size of MCC being the smallest
among the four different grades used should have the minimum
porosity and thus maximum retardation of the release should be caused.
74 M Rahman et al USTA, Vol. 15, No. 1 75
Fig. (2a) : Cumulative percent release vs. Time of formulations
E1- E4. (E1 for MCC1- E4 for MCC4)
Fig. (2c) : Cumulative percent released vs. Square root of time
of formulations E1-E4.
Absorbance Test :
For absorbance test we have used Thermo Electron machine and find out
the lambda properties. Ranitidine HCl released in 0.1N HCl was
estimated at λmax 315 [13]. We have taken 10 samples from the
dissolution machine and place the sample into the UV machine. Then
find the following peak result.
Time interval (mins) Absorbance (AO)
10 0.031
20 0.036
30 0.038
40 0.042
50 0.048
60 0.067
Fig. 3 : Absorbance in respect to time.
Conclusion
The prepared pellets varied in pellet properties such as drug dissolution
profile, size, size distribution, shape, flow properties, densities and
friability. All pellets showed different drug release behaviors. Drug
release occurred by diffusion of the pellet matrix. Mean pellet diameter
did not differ much (P<0.05). All other pellet formulations had almost
similar size. Presence of MCC suppressed the change in mean particle
size. However different MCC grades differed in their circularity
parameters. A linear relationship was found between the pellet
circularity and log bulk density of pure MCC powder. With increase in
density of MCC, roundness decreased. MCC was found to be a very
suitable excipient for the process of extrusion spheronization.
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