b. Emulsion Solvent Diffusion Method: In the emulsion solvent diffusion method the affinity
between the drug and organic solvent is stronger than that of organic solvent
and aqueous solvent. The drug is dissolved in the organic solvent and the
solution is dispersed in the aqueous solvent producing the emulsion droplets
even though the organic solvent is miscible. (The organic solvent diffuse
gradually out of the emulsion droplets in to the surrounding aqueous phase and
the aqueous phase diffuse in to the droplets by which drug crystallizes. [10]
Characterization of the
Optimized Microballoons: -
1.
Determination of bulk density, tapped density and particle density: - Different fractions of the optimized formulation (1g)
were taken into a 10ml
graduated measuring cylinder separately and the volume was noted down. The graduated measuring cylinder was tapped 50 times using USP bulk
density apparatus .The bulk density
and tapped densities were determined using the following formula:
Particle density of
different fractions was determined by the liquid displacement method by suspending the microballoons in a
solvent in which the microballoons were
insoluble like distilled water.
[11]
2.
Particle size analysis: - Particle
size analysis was carried out using the optical microscopic method with the help of a calibrated eye piece micrometer. The size of around
100 particles was measured and median
diameter was calculated. [12]
3.
Scanning Electron Microscopy (SEM): - SEM
was performed for morphological characterization of microballoons using scanning electron
microscope. They were mounted
directly onto the SEM sample stub using double-sided sticking tape and coated with gold film (thickness, 200nm)
under reduced pressure
(0.001mmHg). [13]
4.
In vitro drug release study: - A USP
(United State Pharmacopoeia) basket apparatus has been used to study in vitro drug release from microballoons. In this, drug release was studied using a USP dissolution apparatus
type I at 100 rpm in
distilled water and 0.1 mol HCl (pH 1.2) as dissolution fluid (900 ml)
maintained at 37±0.5°C. Withdrawn samples
were analyzed spectrophotometrically. The volume was eplenished
with the same amount of fresh dissolution fluid each time to maintain the sink
condition. [14]
5. Buoyancy percentage: - Appropriate
amount of microballoons were placed in 900 ml of 0.1 N
hydrochloric acid. The mixture was stirred at 100 rpm in a dissolution apparatus for 8 hrs.
After 8 hrs, the layer of buoyant microballoons were pipetted and separated by filtration. Particles in the sinking particulate layer
were separated by filtration. Particles
of both types were dried in a dessicator until
constant weight. Both
the fractions of microballoons were weighed and buoyancy was determined by the
weight ratio of floating particles to
the sum of floating and sinking particles.
% Buoyancy = [Wf / Wf + Ws)] x 100;
Where Wf and Ws are the weights of the floating and settled
microspheres. [15]
6.
Stability Studies: - During the
storage if one performs studies at normal temp it will take a longer time and hence it
would be convenient to carry out the
accelerated stability studies where the product is stored under extreme conditions of
temperature. Optimized formulation sealed in aluminum packaging coated inside with polyethylene, and various samples were kept in the
humidity chamber maintained at 40°C
and 75% RH for 2 months. At the end of studies, samples were analyzed for the physical
appearance, drug content and drug release.
[16]
7.
Release kinetics: - Data obtained
from in-vitro release studies
were fitted to various kinetic
equations to find out the mechanism of drug release from the ethyl cellulose microsphere.
The kinetic models used were:
Qt = K0 t (zero-order
equation)
ln
Qt = ln Q0 - K1 t (first-order equation)
Qt = Kh
t1/2 (Higuchi equation)
Where Qt is the amount of
drug release in time t, Q0 is the initial amount of drug in the microsphere,
and K0, K1, and Kh are rate constants of zero order,
first order and Higuchi equations, respectively. Further to confirm the
mechanism of drug release, the first 60% of drug release was fitted in Korsemeyer- Peppas model (power
law).
Mt / M∞= k tn
where Mt is the amount of
drug release at time t and M∞ is the amount
release at time t = ∞, thus Mt / M∞ is the fraction of drug released at time t, k is the
kinetic constant, and n is the diffusion exponent which can be used to
characterize both mechanism for both solvent penetration and drug release. [17]
Applications: -
1. Solid and hollow
microballoons vary widely in density and, therefore,
are used for different applications. Hollow microballoons
are typically used as additives to lower the density of a material. Solid microballoons have numerous applications depending on what
material they are constructed of and what size they are.
2. Hollow microballoons can greatly improve the pharmacotherapy of
the stomach through local drug release, leading to high drug concentrations at
the gastric mucosa, thus eradicating helicobacter pylori from the submucosal tissue of the stomach and making it possible to
treat stomach and duodenal ulcers, gastritis and oesophagitis.
3. These microballoons systems provide sustained drug release
behavior and release the drug over a prolonged period of time.
4. The drugs
recently reported to be entrapped in hollow microballoons
include Prednisolone, Lansoprazole,
Celecoxib, Piroxicam, Theophylline, Diltiazem
hydrochloride, Verapamil hydrochloride and
Riboflavin, Aspirin, Griseofulvin, Ibuprofen, Terfenadine.
5. Floating microballoons can greatly improve the pharmacotherapy of
stomach through local drug release. Thus, eradicating Helicobacter pylori from
sub-mucosal tissue of the stomach are useful in the treatment of peptic ulcers,
chronic gastritis, gastro esophageal reflux diseases etc. Hollow microballoons of ranitidine HCl
are also developed for the treatment of gastric ulcer.
6. Floating microballoons are especially effective in delivery of
sparingly soluble and insoluble drugs. It is known that as the solubility of a
drug decreases, the time available for drug dissolution becomes less adequate
and thus the transit time becomes a significant factor affecting drug
absorption. For weakly basic drugs that are poorly soluble at an alkaline pH,
hollow microballoons may avoid chance for solubility
to become the rate-limiting step in release by restricting such drugs to the
stomach. The gastro-retentive floating microballoons
will alter beneficially the absorption profile of the active agent, thus
enhancing its bioavailability.
7. The floating microballoons can be used as carriers for drugs with
so-called absorption windows, these substances, for example antiviral,
antifungal and antibiotic agents (Sulphonamides, Quinolones, Penicillins, Cephalosporins, Aminoglycosides
and Tetracyclines) are taken up only from very
specific sites of the GI mucosa.
8. Hollow microballoons of non-steroidal anti inflammatory drugs are
very effective for controlled release as well as it reduces the major side
effect of gastric irritation; for example floating microballoons
of Indomethacin are quiet beneficial for rheumatic
patients. [18, 19]
CONCLUSION:
In recent review we
concluded that the floating hollow microcapsules showed gastroretentive
controlled release delivery system, promises to be a potential approach for
gastric retention. Although there are number of difficulties to be worked out
to achieve prolonged gastric retention, a large number of companies are
focusing toward commercializing this technique. Hollow microballoons
are low-density, sufficient buoyancy to float over gastric contents and remain
in stomach for prolonged period. As the system floats over gastric contents,
the drug is released slowly at desired rate resulting in increased gastric
retention with reduced fluctuations in plasma drug concentration. Floating
hollow microcapsules of melatonin showed gastroretentive
controlled release delivery system.
REFERENCES:
1.
Dhole
A.R., Gaikwad P.D., Bankar
V.H., Pawar S.P. A Review on Floating Multiparticulate
Drug Delivery
System- A Novel Approach to Gastric Retention IJPSRR.
6 (2); 2011: 205-211.
2.
Somwanshi
S.B., Dolas R.T., Nikam
V.K., Gaware V.M., Kotade
K.B., Dhamak K.B. and Khadse
A.N. Floating Multiparticulate Oral Sustained Release
Drug Delivery System. J.Chem. Pharm
Res. 3 (1); 2011: 536-547.
3.
Patel D.M., Patel M.J., Patel C.N., Multi
Particulate System: A Novel Approach in Gastro-Retentive Drug Delivery. IJAPR.
2 (4); 2011: 96-106.
4.
Audumbar Digambar Mali, Ritesh Suresh
Bathe. A Review on Gastroretentive Floating Drug
Delivery System. American
Journal of Pharmtech Research. 5 (2); 2015: 107-132.
5.
Kawashima Y., Niwa
T., Takenchi H., Hino T., Itoh
Y. Hollow microspheres for use as a floating controlled drug delivery system in
the stomach. J Pharm Sci. 81; 1992: 135-140.
6.
Pujara
N.D., Patel N.V., Thacker A.P., Raval B.K., Doshi S.M., Parmar R.B. Floating
microspheres: a novel approach for gastro Retention. World journal of pharmacy
and pharmaceutical sciences. 1 (3); 2012: 872-895.
7.
Dhole AR., Gaikwad PD., Bankar VH., Pawar
SP. A Review on Floating Multi particulate Drug Delivery System- a Novel
Approach to Gastric Retention. IJPSRR.
6 (2); 2011: 205-211.
8.
Somwanshi SB., Dolas RT., Nikam VK., Gaware VM., Kotade KB., Dhamak KB., Khadse AN. Floating Multiparticulate
Oral Sustained Release Drug Delivery System. J.Chem.Pharm Res. 3 (1); 2011: 536-547.
9.
Kunchu K., Ashwani RV., Albumin
Microspheres: A Unique system as drug delivery carriers for non-steroidal anti-inflammatory
drugs. 5 (2); 2010: 12.
10.
Joshi VK., Jaimini M. Microballons
drug delivery system: A review. AJPRD.1
(1); 2013 :7 –17.
11.
Awasthi
R, Kulkarni GT. Development and characterization of
amoxicillin loaded floating microballoons for the
treatment of Helicobacter pylori induced gastric ulcer. Asian J of Pharma Sci. 8; 2013:174-180.
12.
Chandrakala
V, Saral AM. Quality by
design approach in formulation of bioadhesive levodopa microspheres. Int J of
Pharmacy and Pharm Sci. 5 (4); 2013: 172-178.
13.
Yadav
VK, Kumar B, Prajapati SK, Shafaat.
Design and evaluation of mucoadhesive microspheres of
repaginate for oral controlled release. Int J of Drug
Delivery. 3; 2011: 357-370.
14.
Yadav
A, Jain DK. Gastroretentive microballoons
of metformin: Formulation Development and Characterization.
J of adv Pharma Tech and Res. 2 (1); 2011: 51-56.
15.
Aphale
S, Shinde S, Dhat S, Bagul U, Saluja J. Development
and evaluation of hollow microspheres of Clarithromycin
as a gastroretentive drug delivery system using eudragit polymers. Int J of Pharma and Bio Sci. 2 (3); 2011: 344-355.
16.
Gandhi NS, Shirolkar
SV, Tawar MG. Development and evaluation of microballoons of pioglitazone
hydrochloride using Eudragit S-100. 3 (1); 2012:
201-212.
17.
Bansode
SD, Kasture VS, Pawar SS, Kasture SB. Formulation and evaluation of telmisartan microspheres by emulsion solvent evaporation
technique. Journal of Applied Pharmaceutical Science. 2 (10); 2012: 113-116.
18.
Pujara ND., Patel NV., Thacker AP., Raval
BK., Doshi SM., Parmar RB.
Floating microspheres: a novel approach for gastro Retention. World J. of Pharmacy and Pharmasci.
1 (3); 2012: 872-895.
19.
Moursy NM., Afifi NH., Ghorab DM., El-Saharty Y.
Formulation and evaluation of sustained release floating capsules of Nicardipine hydrochloride. Pharmazie. 58; 2003: 38-43.
Received on 03.07.2015 Accepted
on 02.08.2015
© Asian Pharma Press All
Right Reserved
Asian J. Res. Pharm. Sci.
5(3): July-Sept.; Page 188-192
DOI: 10.5958/2231-5659.2015.00028.4