Formulation and evaluation of nanosuspension drug delivery system for poorly soluble drugaceclofenac
Available online on www.ijcpr.com (ISSN: 0976 822X)
International Journal of Current Pharmaceutical Review and Research
Volume 1, Issue 3, November 2010 - January 2011
Research Article Formulation, Development and Evaluation of floating tablet of Metformin Hydrochloride using optimization of gas generating agent
Department of Pharmaceutical Sciences, Jaipur National
Abstract: The present study deals with drug release enhancement of Metformin
Hydrochloride using floating technology by optimization of gas generating agent to improve
the buoyancy time. Metformin hydrochloride is a oral antihyperglycemic agent of biguanide
class used in treatment of type 2 Diabetes. It is hydrophilic drug which absorbed slowly and
not completely form the gastrointestinal tract. The absolute bioavailability is reported to be
50-60%. This technology uses direct compression method to prepare floating tablet of
Metformin Hydrochloride with release retardant polymer HPMC K-100, PVP K-30, Carbopol
934p and different concentration of gas forming agents sodium bicarbonate and citric acid.
The floating behavior and in vitro dissolution studies ware carried out. From the result final
formulation release was found to be approximately 96% in 24 hr, while the floating lag time
was observed to be 3 min and the tablet remained floatable throughout studies. Form the
result of the study we conclude that incorporation of gas generating agent produced initial
burst-effect due to production and release of CO2 form polymeric matrix. Increased concentration of sodium bicarbonate results in increased bursting effect. Optimum
concentration of sodium bicarbonate was found to be 8-10% to produce low floating lag time.
Thus, with using of optimum concentration of gas generating agent the floating tablet of
Metformin Hydrochloride was successfully developed.
Key words: Metformin hydrochloride, sodium bicarbonate, floating lag time
Corresponding author Email: [email protected]Introduction
During the last decade, many formulations have been performed concerning sustained release
mechanisms of drugs. Orally administration of drug is the predominant and most accepted
route for drug delivery because of several advantages like patients compliance, easy to
administration etc. amongst the sustained release, the floating drug delivery system of drug is
predominant method for sustained release of Metformin hydrochloride. Depending on the
mechanisms of buoyancy, two different methods viz., effervescent and non-effervescent
systems have been used in the development of floating drug delivery system. Effervescent
methods utilize polymer metrics like HPMC K100, Carbopol 934p, and gas generating agent
like sodium bicarbonate, citric acid. Proper optimization of gas generating agent is important
Metformin Hcl is a biguanide antihyperglycemic agent that improves glucose tolerance in
patients with type II diabetes. Metformin Hydrochloride is incompletely absorbed from
gastrointestinal tract, it has absorption window confined to upper part of gastrointestinal tract
.It has half life of 1.7 hours and its absolute bioavailability is reported to be about 45-50% of
the administered dose, hence it is a suitable candidate for gastroretentive floating drug
Materials and Methods
Metformin hydrochloride and HPMC K 100were received as gift sample from JCPL
pharmaceuticals Pvt. Ltd., jalgaon. Sodium bicarbonate and citric acid was purchased form
Preparation of floating tablet
1) Weigh accurately Metformin hydrochloride, HPMC K 100, PVP K 30, Carbopol 934p
and talc according to formula given in table 1.
2) Then passed all above materials through different required sieve for uniformity.
3) Mix the drug with all above excipient geometrically for 10 min to achive homogeneous
4) The mixed the Magnesium stearate with above homogeneous blend for 3 min.
5) Tablet ware prepared by direct compression technique using cadmach single punch
IJCPR, Nov 2010 – Jan 2011 Table 1: Ingredients of different Batch Numbers Ingredients (mg per tablet) Batch No. Metformin hydrochloride HPMC K 100M Carbopol 934p Sodium bicarbonate Citric acid Magnesium stearate Figure 1: Standard curve of Metformin hydrochloride at 233nm Conce ntration Evaluation of tablet (1) Floating lag time
The tablets were placed in a 100ml beaker containing 0.1 N HCL and the time
required for the tablet to rise to the upper surface is noted.
(2) In-vitro dissolution study IJCPR, Nov 2010 – Jan 2011
The Metformin Hydrochloride release from different bi-layer formulation was determined
using USP Type-2 apparatus under sink condition. The dissolution medium was 900ml
simulated gastric fluid (pH 1.2, no enzyme) at 37+ 5 ̊C, paddle speed 50rpm to
stimulate in-vivo condition. The formulation was subjected to dissolution test for 24
hr. Sample(5ml) was withdrawn at predetermined interval, filtered through whatmann
filter paper and replaced by an equal volume of dissolution medium. Drug content in
the dissolution sample was analyzed at 233mm by using UV spectrophotometer.
Table 2: Floating lag time of A,B,C batch Floating lag time Total floating time Table 3: Dissolution profile of A,B & C Batch % Concentration IJCPR, Nov 2010 – Jan 2011 (3) Floating time
The total floating time of tablet was studied in USP type-2 dissolution apparatus a at
37+ 5 ̊C in 900ml simulated gastric fluid (pH 1.2, no enzyme). The time of floatation
Figure 2: Floating lag time of A,B & C batch Figure 3 Dissolution profile of Different batch A, B & C Tim e(hr) Result and Discussion
The floating tablet of Metformin Hydrochloride using optimization of different gas forming
agent, Sodium bicarbonate and citric acid was prepared and evaluated for lag time, total
IJCPR, Nov 2010 – Jan 2011
floating time and drug release profile to increase its bioavailability and its local action. In the
present study three formulations were prepared using different concentration of sodium
bicarbonate and citric acid and evaluated for lag time.
On the immersion in a 100ml beaker containing 0.1 N HCL solution the tablets were
float by bursting effect of gas forming agent. Incorporation of gas generating agent
produced burst-effect due to production and release of generated CO2 from polymer matrix. Higher concentration of sodium bicarbonate results into higher bursting effect.
All formulated batches (A, B & C) passed the weight variation test, hardness test, friability
and physical characteristics. Increase in hardness will decrease the porosity of the tablet and
ultimately to the water penetration and floating lag time. In such cases, it would be necessary
to go up to 10% sodium bicarbonate to get a low floating lag time in presence of other
excipients. Formula A contains 5% sodium bicarbonate and 5% citric acid. Formula B
contains 7.5% Sodium bicarbonate and 2.5% citric acid and Formula C contains 8.75 sodium
bicarbonate and 1.25% citric acid. Formula A showed high floating lag time compared to
formula B. Formula C showed less floating time as compared to formula B but high bursting
effect than Formula A and B. Formula B is optimum for floating of tablet that showed less
floating lag time and less bursting effect.
The floating tablet of Metformin Hydrochloride with polymer and different concentration of
gas forming agent was formulated. Formula B was found to be .optimum. Thus it was
conclude to use sodium bicarbonate 8-10% to get least floating.
M.M varma et al, Formulation and Evaluation of floating drug delivery system of
Metformin Hydrochloride, Journal of Chemical and pharmaceutical research, 2010,
Ziyaur rahman et al, Design and evaluation of floating tablets of captopril, Acta pharm,
Ravindra S Dhumal et al, Design and evaluation of bilayer floating of cefuroxime axetil
bimodal release, Journal of scientific and research, vol 65, oct.2006, 812-816.
Timmermans, J., Moës, A.J., 1990. How well do floating dosage forms float? Int. J.
IJCPR, Nov 2010 – Jan 2011
Baumgartner, S., Smid-Korbar, J.,Vrecer, F., Kristl, J., 1998. Physical and technological
parameters influencing floating properties of matrix tablets based on cellulose ethers.
Rosa M, Zia H, Rhodes T, Dosing and testing in-vitro of a bioadhesive and floating
drug delivery system for oral application, Int. J. Pharm; 1994,105:65-70.
K Raghuram Reddy, Srinivas Mutalik, Srinivas Reddy, Once-daily sustained release
matrix tablets of Nicorandil: Formulation and in vitro evaluation, AAPS PharmSciTech;
Aulton ME, Wells TI, Pharmaceutics: The Science of Dosage Form Design. London,
England, Churchill Livingston; 1998;247.
Cooper J, Gun C, Powder Flow and Compaction. Inc Carter SJ, Eds. Tutorial Pharmacy.
New Delhi, hidix CBS Publishers and Distributors; 1986:211-233.
10) Chatwal, G R., Anand S K., Instrumental Methods of Chemical Analysis (Analytical
chemistry). Fifth revised and Enlarged edition, Himalaya Publishing House: 2.29-2.82,
11) Chein YW. Novel Drug Delivery Systems. 2nd ed. Vol 50. New York: Marcel Dekker.
12) Yeole PG, Khan S, Patel VF. Floating drug delivery system: need and development. Ind
13) Talukder R, Fassihi R. Gasroretentive delivery system: A mini review. Drug Dev Ind
14) Shirwaikar AA, Kumar SMR, Jacob S, Rashi W, Ravi K, Recent development in
floating drug delivery system for gastric retention of drugs, an overview. Ind Drugs
15) Jain NK. Pharmaceutical product development. 1st ed. Delhi: CBS Publication and
IJCPR, Nov 2010 – Jan 2011
Flu Widespread in Kentucky Judy Mattingly Health Department Each year approximately 23,000 people die of the flu in the U.S. Earlier this month the Kentucky Department for Public Health announced that influenza or flu had become widespread in Kentucky. Widespread is the highest level of flu activity and indicates increased activity or outbreaks in at least half of the regions in a state. At least
MANAGEMENT OF GASTRIC OUTFLOW OBSTRUCTION IN FOALS Rood and Riddle Equine Hospital, Lexington, Kentucky Equine gastric ulcer syndrome is common in performance horses and foals. The clinical syndromes of gastric ulceration are age dependant. In neonates the glandular mucosa is most often involved. Clinical signs in foals as are follows: diarrhea, abdominal pain, intermittent nursing, weight l