Formulation and In-Vitro Evaluation of Floating Tablet
of Gabapentin
Nihar Ranjan Kar1*, Santosh
Kumar Mahapatra2, Rajesh Kumar Pothal2, Chaitanya Pr.
Meher1
1Department of Pharmaceutics, Gyan Vihar, Gayatri
Institute of Science and Technology (GIST) Gunupur, Dist- Rayagada, 765022
Odisha.
2Dept. of Pharmaceutics, Gayatri College of Pharmacy,
Sambalpur, Odisha.
*Corresponding Author E-mail:
nihar_795@rediffmail.com
ABSTRACT:
The present research work is an attempt to formulate
rate controlled drug delivery system of Gabapentin which is primarily absorbed
from stomach, so by increasing the GRT of the drug, the bioavailability can be
increased. As the drug is stable in acidic pH and mostly absorbed with in pH
1-3, as the stomach is the major absorption site for the drug. Basing on this
fact the drug is made to float in the stomach using the mechanism of buoyancy.
The study also includes various evaluation studies of Gabapentin tablet and the
effect of processing variables on it. A possible interaction between drug and
polymers are also investigated by FTIR and DSC studies. So, the present work
has been under taken with the objective of designing and evaluation of floating
oral sustained release tablet drug delivery system of Gabapentin by using HPMC
K15, NaCMC, Xanthun gum, sodium bicarbonate, citric acid. Lactose, ethyl
cellulose etc.
KEYWORDS: Gastric
residence time (GRT), Gastric emptying time (GET), Sustained release,
Drug release kinetics, Gabapentin.
INTRODUCTION:
The goal of any drug delivery system is to provide and
maintain the desired drug concentration within its therapeutic range to its
proper site of action at a predetermined rate dictated by the needs of the body
over the period of time. This idealized objective points to the two aspects,
namely spatial placement and temporal delivery of a drug1. An appropriately designed sustained -/controlled release drug delivery
system can be a major advantage towards solving these two problems. Gastro retentive floating tablet have emerged as an efficient means of
enhancing the bioavailability and controlled delivery of many drugs the
increasing sophistication of delivery technology will ensure the development of
increasing number of gastro-retentive drug delivery systems to optimize the
delivery of molecules that exhibit low absorption window, low bioavailability,
and extensive first pass metabolism2,3
MATERIALS AND METHOD:
Materials:
All the chemicals used were of pharmacopeia grade. Analytical Electronic Balance- Ohaus, AdventurerTM,
India, Hot air oven-NSW, India, Rotary Punch Machine (8 station) -CIP, Lab Press. India., pH meter
Apparatus- ELICO India, Model:-LI 120, 8 Stage Dissolution
Apparatus- Electrolab, Model:-TDT-08 L, USP, HPLC-
Shimadzu, Model:-LC 20AT Prominence, FTIR-Spectrophotometer:
NEXUS 870 FTIR [Thermo Nicolet], Differential Scanning Calorimeter Perkin Elmer
[Pyris Diamond DSC] USA
Fig-5: Hixon plot Calibration curve of Gabapentin
Fig -6: Calibration curve of Gabapentin
Fig:7 Assay of formulation F7
through HPLC
Fig:8 Assay of formulation F8 through HPLC
FTIR study
Fig-9: FTIR Study of formulation F8
Fig-10 : FTIR Study of formulation F7
DSC Study
Fig-11: Comparative DSC graph Gabapentin, F7and F8
Fig- 12: DSC of Formulation -7 [Drug/Nacmc(1/0.5)+ Lactose]
Fig-13: DSC of Formulation -8 [Drug/Nacmc(1/0.25)]
RESULTS AND DISCUSSION:
Drug Content of various Formulations:
The percentage drugs content of Gabapentin in the
floating tablet were shown in table-2 .The formulation F6 showed
highest drug retained value i.e. 98.36% and F1 showed lowest drug
retained value i.e. 50.29%.
Floating ability/ buoyancy of tablet :
The Gabapentin floating tablet was shown to give good
floating ability. Each tablet shows 36hrs floating efficiency except F3
and F6 because the formulation F3 and F6
contains xanthun gum which was shown 12hrs floating action only due to its
swelling nature.
Effect of Sodium Carbonate on floating :
The floating lag time of each formulation decreased
with increase the concentration of sodium carbonate and the total floating time
increases with increase in conc. of NaHCO3.
Effect of Citric Acid on Floating:
Similarly the more amount of citric acid increases the
floating time and decreases floating lag time.
In vitro Release Behavior of Drug:
In this experiment different formulations F1,
F3 were prepared, t50 values lies beyond 12 hrs. In F2
formulation the t50 is about 6-7 hrs and the highest drug
release is 57% at 11hrs, and it was decreasing its release profile at 12hrs
i.e. 54% .similarly like that F4 at 11hrs it is 56.3% but at 12 hrs it is 65%.
But in the formulation F1, F3, F4 the drug release profile is very slow i.e. at
12hrs it is only 26% I F1, 44% in F3 and F4 it is 65% at 12hrs. In these above
formulation F1, F4 having polymer PMCE15LV at different ratio with drug which
have low release profile of drug but in formulation F7 and F8, the dug release
profile is 91.5%in 12 hrs and F8 is 82% at 21hrs and obeying first order
release kinetics with correlation factor 0.985021and 0.9683055 respectively
giving sustained action. F7 and F8 containing the polymer Na CMCI the ratio
with the drug is 1:0.5 and 1:0.25. In F8 which contain less polymer than F7 and
giving more sustaining action because F7 containing lactose which increases the
aqueous entrapment to the formulation. But the F7 formulation show
greater drug release in 12 hrs i.e. 91%.so here it was concluded that the rate
of drug release from all the formulations were sustained as the increase in the
polymer conc. The drug release kinetics in all formulation was different due to
their differences in composition. The drug release was more sustained in F1
where as it was less sustained in F7. The reason behind the
differentiation in drug release kinetics was based upon nature of polymers and
the drug polymer ratio. From the linearity data of Higuchi equation mention in
the Table-6, it was conclude that all formulation are obeying Higuchi equation
i.e. In all formulation the drug was released in diffusion process.
IR spectrum Study :
The polymer, drug and the formulation structure was
confirmed by IR spectroscopy. The IR Spectra of NaCMC, it is evident that it
shows a broad observation band at 3408.21cm-1, due to the stretching frequency
of –OH group. The band at 2922.26 cm-1 is due to C-H stretching vibration. The
presence of strong observation, band at 1598.04 cm-1 confirms the presence of
COO group. The band around 1418.13 cm-1 and 1326.89 cm-1 are assigned to –CH2
scissoring and –OH bending vibration, respectively. The band at 1060.44 cm-1 is
due to >CH-OCH2 stretching. The IR spectra of Gabapentin, It shows abroad
observation band at 2931.75 cm-1 due to C-H stretching of cyclohexane. The
presence of strong observation band at 1459.07 cm-1 indicates C-H bending in
cyclohexane (saturated) six membered ring. The band at 1328.48 cm-1 indicates
the presence of C-O stretching for carboxylic acid and the band at 1421.75 cm-1
indicates the C-O-H bending. The band at 1298.27 cm-1 indicates the presence of
C-N bond stretching and the band at 1650.46 cm-1 indicates the presence of N-H
(scissoring) vibration. From the above given data It is concluded that, in the
formulation F7, F8 there was no interaction between the drug and polymer.
DSC STUDY :
The present study describes the application of
differential scanning calorimetry (DSC) to ascertain the crystalline state of a
drug with a melting point of 173.02°C after dispersion on hydrophilic carriers
by either simple mixing or by fusion. Whereas in formulation F7 and F8 the
melting point range was found 138.2oC to 146.31oC. The
most interesting of the systems investigated, in which the drug is gradually
transformed from the crystalline to the amorphous state at high temperature so
it helps to increase drug solubility.
CONCLUSION:
In the present work described, ‘Formulation and
Evaluation of Floating Tablet of Gabapentin’ it was used different polymers
(NaCMC, Xanthun Gum and HPMC K15 LV) with effervesce ting agents like sodium
bicarbonate and citric acid for designing a floating tablet using wet
granulation technique. Among the all formulation, F8 showed better sustained
released product. As this formulation have good floating ability more than 36
hour, more percentage of drug content i.e. 87% and showed more than 12 hour of
drug release through diffusion process with first order rate profile. From the
FTIR study the above formulation have no drug - polymer interaction and from
DSC study the amorphous state of drug was change its property to crystalline
and increase solubility. So, the formulation F8 was more effective in the
epilepsy management owing to better pharmacological response.
REFERENCES:
1.
Jantzen, Gwen M.,
Robinson, Joseph R.; Sustained- and Controlled Release drug delivery systems,
Modern pharmaceutics,3rd Edition, Revised and Expanded, Edited by Gilbert S.
Banker, Christopher T. Rhodes; Drugs and Pharmaceutical Sciences, Volume 12, P 578-579.
2.
Davis, Stanley S.,
Institute of Pharmaceutical Sciences, University of Nottingham, University
Park, Nottingham, UK, NG7 2RD, Formulation Strategies For Absorption Window;
Drug Discovery Today(DDT), Volume-10,Number 4, February 2005
3.
Lachman, Leon.,
Lieberman, H.A., Kanig, J.L., Sustained Release Dosage Forms, In; The Theory
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