1Department of Pharmaceutics, M.L. College of Pharmacy, S. Konda-523101
2 Assistant professor, Department of Pharmaceutics, M.L. College of Pharmacy, S. Konda-523101.
3 Head, Department of Pharmaceutics, M.L. College of Pharmacy, S. Konda-523101.
Abstract
Gastro retentive drug delivery systems have been widely used to prolong the retention of dosage forms in the stomach. Among the various approaches, the floating in-situ gelling formulation offers sustained drug release as well as prolonged gastric retention, along with the added advantage of the liquid oral dosage form. The present study was an attempt to formulate and evaluate floating in situ gel of Eplerenone by using various polymers like Xanthan gum, Carbopol, HPMC K100M, and Karaya gum which undergoes pH dependent sol-gel transition at gastric pH, thereby prolonging the retention of the system in the stomach. Sodium alginate a natural polymer was employed as a gelling agent where Gelation is triggered by the source of calcium ions in the form of calcium carbonate. Drug and polymers were subjected for compatibility study using FTIR studies, which revealed that there was no interaction between drugs and polymers. The evaluation was carried out for invitro parameters such as gelling nature, Total floating time, drug content, viscosity, & in vitro dissolution studies. Among all the formulations, the F12 formulation containing HPMC K100M was chosen as an optimized formulation that shows maximum drug release by the end of 12hrs and has excellent floating characteristics and gastric retention. From kinetic studies, the optimized formulation shows zero-order release with super case II transport mechanism.
Keywords: In situ gel, pH dependent sol-gel transition, Eplerenone, Sodium alginate, Calcium carbonate.
Article History
Received on: 28-04-2021
Revised on: 13-05-2021
Accepted on: 08-06-2021
*Corresponding Author
M.Parthy
Email: malyapharma22@gmail.com
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Introduction
The development of in situ gelling systems has received considerable attention over the past few years. In situ gel forming drug delivery systems are principle, capable of releasing drug in a sustained manner maintaining relatively constant plasma profiles. These hydrogels are liquid at room temperature but undergo gelation when in contact with body fluids or change in ph. These have a characteristic property of Temperature dependent, Ph dependent and action induced gelation. Compared to conventional controlled release formulations, in situ forming drug delivery systems possess potential advantages like simple manufacturing process, ease of administration, reduced frequency of administration, improved patient compliance and comfort.1-2Insitugel forming drug delivery is a type of much adhesive drug delivery system. In contrastively strong gels, they can be easily applied in liquid form to the site of drug absorption. At the site of drug absorption they swell to form a strong gel that is capable of prolonging the residence time of the active substance. Both natural and synthetic polymers can be used for the production of insitu gels. In situgel formation occurs due to one or combination of different stimuli like pH change, temperature modulation and ionic cross-linking3-5. So, insitu gels are administered by oral, ocular, rectal, vaginal injectable and intra-peritoneal route recent advances in insitu gels have made it possible to exploit the changes in physiological uniqueness in different regions of the GI tract for the improved drug absorption as well as patient’s convenience and compliance [6].
Advantages of in-situ gels [6-7]
Disadvantages [7]
Ex: Aspirin and non-steroidal anti-inflammatory drugs Eplerenone 8, an aldosterone receptor antagonist similar to spironolactone, has been shown to produce sustained increases in plasma renin and serum aldosterone, consistent with inhibition of the negative regulatory feedback of aldosterone on renin secretion. The resulting increased plasma renin activity and aldosterone circulating levels do not overcome the effects of eplerenone. Eplerenone selectively binds to recombinant human mineralocorticoid receptors relative to its binding to recombinant human glucocorticoid, progesterone and androgen receptors.
Fig o1:Chemical Structure of Eplerenone
Materials
Eplerenone from BMR Chemicals, Hyderabad, Sodium alginate from Color cone Asia Ltd., Verna, Goa, Calcium carbonate, Sodium citrate, Ethyl cellulose MJ Biopharmaceuticals, Mumbai, HPMC K4M,Carbopol 934 from Otto Chemicals, Hyderabad Water Narmada chemicals
Methods
Preformulation studies [9-13]
Solubility studies
Solubility of Eplerenone was determined in Methanol, Ethanol, pH 1.2, pH 6.8 and pH 7.4 phosphate buffers. Solubility studies were performed by taking excess amount of Eplerenone in different beakers containing the solvents. The mixtures were shaken for 24 hrs at regular intervals. The solutions were filtered by using whattmann’s filter paper grade no. 41. The filtered solutions were analyzed spectrophotometrically at 244 nm.
Drug-excipient compatibility study
The physical compatibility between the pure drug and polymers used in the research was tested by Infra Red (IR) spectroscopy. FTIR absorption spectra for pure drug and physical mixture were recorded in the range of 400-4000cm -1 by KBr disc method using FTIR spectrophotometer.
Determination of Absorption maxima by UV spectrophotometer
10mg of Eplerenone was dissolved in 2ml of methanol then makeupto10ml with 6.8pH buffer so as to get a stock solution of 1000 µg/ml concentration. From the above stock solution pipette out 1ml of the solution and makeup the volume to 10ml using 6.8pH buffer to get the concentration of 100µg/ml concentration. From this stock solution pipette out 1ml of the solution and makeup the volume to 10ml using 6.8pH buffer to get the concentration of 10µg/ml concentration, this solution was scanned under UV Spectroscopy using 200-400nm.
Preparation of calibration curve of Eplerenone
10mg of Eplerenone was accurately weighed and transferred into 10ml volumetric flask. It was dissolved and diluted to volume with pH 1.2 Acidic buffer to give stock solution containing 1000µg/ml. The standard stock solution was then serially diluted with pH 1.2 Acidic buffer to get 2 to 12µg/ml of Eplerenone. The absorbance of the solution were measured against pH 1.2 Acidic buffer as blank at 244nm using UV visible spectrophotometer. The absorbance values were plotted against concentration (µg/ml) to obtain the standard calibration curve.
Method of Preparation of In-situ Gel
Floating in situ gel formulations of Eplerenone were prepared using compositions given in Table .Take 100ml beaker, in that beaker take sodium alginate and add with polymer, then mix with 60ml distilled water, now heat the mixture at 60?C till solution occurs using a heating magnetic stirrer .Take another 100ml beaker, in this add sodium citrate along with calcium carbonate, then mix with 30ml distilled water, heat the mixture at 60?C till solution occurs. Now take another beaker, add 5ml methanol with drug, then three mixtures are mixed at 60?C. After cooling this solution below 40?C, keep the above mixture in mechanical stirring for 30 minutes, well to get the final preparation which was stored in amber colour bottles until further use [14-18]
Table 01: Formulation of Eplerenone Oral Insitu Gels
|
Ingredients (g) |
F1 |
F2 |
F3 |
F4 |
F5 |
F6 |
F7 |
F8 |
F9 |
F10 |
F11 |
F12 |
|
Eplerenone |
0.5 |
0.4 |
0.4 |
0.4 |
0.4 |
0.4 |
0.4 |
0.4 |
0.4 |
0.4 |
0.4 |
0.4 |
|
Sodium alginate |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
|
Calcium carbonate |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
|
Sodium citrate |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
|
Ethyl cellulose |
0.25 |
0.5 |
0.75 |
1 |
-- |
-- |
-- |
-- |
-- |
-- |
-- |
-- |
|
Carbopol 934 |
-- |
-- |
-- |
-- |
0.25 |
0.5 |
0.75 |
1 |
-- |
-- |
-- |
-- |
|
HPMC K4M |
-- |
-- |
-- |
-- |
-- |
-- |
-- |
-- |
0.25 |
0.5 |
0.75 |
1 |
|
Water (ml) |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
Evaluation parameters of oral in-situ gels
Visual Appearanceand Clarity
Visual appearance and Clarity was doneunder fluorescent light against a white and black back ground for presence of any particulate matter.
pH Measurement
The Ph of the preparedin-situ gell in gsystem after addition of all the in gredients was measured using pH meter.
Determination of drug content
Accurately 5mL of formulation from different batches was measured and transferred to 100 mL volumetric flask. To this 50-70mL of 0.1 N HCL was added and sonicated for 30 min. Volume was adjusted to 100mL. Complete dispersion of contents was ensured visually and the dispersion was filtered using Whattman Filter Paper. From this solution, 1 mL of sample was withdrawn and diluted to 10mL with 0.1 N HCL. Contents of Eplerenone was measured at maximum absorbance at 266 nm using UV-Visible Spectrophotometer. [T60 PG INSTRUMENTS]
In vitro floating study
The in-vitro floating study was carried out by introducing 5 mL of formulation into a beaker containing 100 ml of 0.1N HCl, (pH 1.2) at 37?C without much disturbance. The time the formulation constantly floated on surface of the dissolution medium (duration of floating) were recorded.
In-vitro gelation study
To evaluate the formulations for their in-vitro gelling capacity, accurately measured 5 mL of formulation was added to 100 mL of 0.1N hydrochloric acid (HCl, pH 1.2) at 37?C in a beaker with mild agitation that avoids breaking of formed gel.
The in vitro gelling capacity was graded in three categories on the basis of stiffness of the formulation.
(+) Gels after few minutes, dispersed rapidly
(++) Gelation immediate remains for few hours
(+++) Gelation immediate remains for an extended period.
Measurement of viscosity of in-situ gelling system
Viscosity of the dispersion was determined using a Brookfield digital viscometer (NDJ-5S Viscometer). The samples (5 mL) were sheared at a rate of 10 rpm/min using spindle number 2 at room temperature. Viscosity measurement for each sample was done in triplicate, with each measurement taking approximately 30 seconds.
In-Vitro Release Studies
The drug release study was carried out using USP type II paddle type apparatus at 37 ± 0.5ºC and at 50 rpm using 900 ml of 0.1 N HCl (pH 1.2). In situ gel equivalent to 20 mg of Eplerenone was used for the test. Sample solution (5 ml) was withdrawn at predetermined time intervals, filtered through a 0.45 μm membrane filter, diluted and suitably analyzed by UV spectrophotometric LABINDIA 8000 at 266 nm. Fresh dissolution medium was replaced immediately after withdrawal of the test sample to maintain sink condition. The dissolution studies were carried out for a period of 12 h.
Release Kinetics [19-20]
In the present study, data of the in vitro release were fitted to different equations and kinetic models to explain the release kinetics of Eplerenone from the insitu gels. The kinetic models used were Zero order equation, First order, Higuchi release and Korsmeyer-Peppas models.
Kinetic Studies: Mathematical models:
Different release kinetic equations (zero-order, first-order, Higuchi's equation and Korsmeyer-peppas equation) were applied to interpret the release rate of the drug from matrix systems for the optimized formulation. The best fit with higher correlation (r2) was calculated.
Zero-order model
Drug dissolution from dosage forms that do not disaggregate and release the drug slowly can be representedby the equation
Qt = Q0 + K0t
Where Qt is the amount of drug dissolved in time t, Q0 is the initial amount of drug in the solution (most times, Q0 = 0) and K0 is the zero order release constant expressed in units of concentration/time. To study the release kinetics, data obtainedfromin vitro drug release studies were plotted as cumulative amount of drug released versustime.
Application: It is used to describe the drug dissolution of several types of modified release pharmaceutical dosage forms, as in the case of some transdermal systems, as well as tablets with low soluble drugs in coated forms, osmotic systems, etc.
First Order Model
The first order equation describes the release from systems where the dissolution rate is dependent upon the concentration of the dissolving species.
Release behavior generally follows the following first order equation:
Log C= Log Co-kt/2.303
Where C is the amount of drug dissolved at time t,
Co is the amount of drug dissolved at t=0 and
k is the first order rate constant.
A graph of log cumulative of % drug remaining vs time yields a straight line.
The pharmaceutical dosage forms following this dissolution profile, such as those containing water-soluble drugs in porous matrices, release the drugs in a way that is proportional to the amount of drug remaining in its interior, in such way, that the amount of drug released by unit of time diminishes.
Higuchi model
The first example of a mathematical model aimed to describe drug release from a system was proposed by Higuchi in 1961. Initially conceived for planar systems, it was then sustained to different geometrics and porous systems. This model is based on the hypothesis that
In a general way the Higuchi model is simply expressed by following equation
Q = KH - t1/2
Where, KH is the Higuchi dissolution constant.
The data obtained were plotted as cumulative percentage drug release versus square root of time.
Korsmeyer-Peppasmodel
Korsmeyer et al. (1983) derived a simple relationship which described drug release from a polymeric system equation. To find out the mechanism of drug release, first60% drug release data were fitted in Korsmeyer-Peppas model,
Mt / M∞ = Ktn
where Mt / M∞ is a fraction of drug released at time t, k is the release rate constant and n isthe release exponent. The n value is used to characterize different release for cylindrical shaped matrices. In this model, the value of n characterizes the release mechanism of drug as described in the following table.
Table 02: Drug transport mechanisms suggested based on ‘n’ value
|
S.No |
Release exponent |
Drug transport mechanism |
Rate as a function of time |
|
1 |
0.5 |
Fickian diffusion |
t -0.5 |
|
2 |
0.45 < n = 0.89 |
Non -Fickian transport |
t n-1 |
|
3 |
0.89 |
Case II transport |
Zero order release |
|
4 |
Higher than 0.89 |
Super case II transport |
t n-1 |
The results of invitro release profiles obtained for the insitu gels formulations were fitted into four models of data treatment as follows:
Results and discussion
Saturation Solubility of Eplerenone
Solubility of Eplerenone was determined in 0.1 N HCL, 7.4 pH buffer, & 6.8 phosphate buffer and values obtained were noted in the table given below.
Table :3 Solubility studies of Eplerenone in various solvents
|
Solvents |
Solubility(µg/ml) |
|
0.1 N HCL or 1.2pH Acidic buffer |
0.559 |
|
6.8 pH buffer |
0.262 |
|
7.4pH buffer |
0.244 |
Fig :2 Solubility studies of Eplerenone
From the above solubility data we can say that Eplerenone has more solubility in 0.1N HCl or 1.2 pH Acidic buffer.
Compatibility study of Eplerenone
Compatibility between the drug and polymers was studied by FT-IR method. Pure Eplerenone and optimized formulation were subjected for FT-IR spectroscopic analysis, to ascertain any interaction between the drug and polymers used. The position of characteristic peaks of pure Eplerenone was compared with thosepeaks obtained for optimized formulation. These characteristic bands for Eplerenonewere identifiable and there was no major shift or disappearance in the peak positions.This indicated that the drug was intact and has not reacted with the excipients used in the formulation and hence they are compatible. Hence, it can be concluded that the drug is in free-state and can release easily from the polymeric network in the free form.
Fig 03: FTIR graph of pure Eplerenone
Fig 04: FTIR graph of optimized formulation
Determination of absorption maximum (λmax) of Eplerenone
Determination of Eplerenone λ-max was done for accurate quantitative assessment of drug dissolution rate.
Fig 05: Absorption maximum (λmax) of Eplerenone 266 nm
Standard calibration curve of Eplerenone
Table 4:Calibration curve dataEplerenone in 0.1N HCl
|
Concentration (µg/ml) |
Absorbance |
|
0 |
0 |
|
5 |
0.138 |
|
10 |
0.264 |
|
15 |
0.426 |
|
20 |
0.551 |
|
25 |
0.691 |
|
30 |
0.816 |
Fig 06: Calibration curve of Eplerenone in 0.1N HCl
Eplerenone beer’s range concentration was found to be in the range of 5-30 µg/ml using 0.1 N HCL buffer as buffer solution. The regression value was closer to 1 indicating the method obeyed Beer-lamberts’ law as it was linear.
Drug content
Table 05: Percentage Drug content of Eplerenoen insitu gels
|
Formulation code |
Drug content(%) |
|
F1 |
95.53 |
|
F2 |
96.76 |
|
F3 |
97.34 |
|
F4 |
95.85 |
|
F5 |
98.46 |
|
F6 |
99.45 |
|
F7 |
97.72 |
|
F8 |
100.73 |
|
F9 |
97.52 |
|
F10 |
98.45 |
|
F11 |
96.82 |
|
F12 |
98.48 |
Discussion
The drug content was found to being the range of 95.53-100.73% for all the formulations indicating uniform distribution of drug.
In Vitro Gelation study
Gelling studies were carried out using 0.1N HCl and the obtained data were represented in Table. All formulations showed immediate Gelation upon contact with acidic medium and the formed gel preserved their integrity. Gelation occurs when the insoluble calcium carbonate solubilises when it comes in contact with acidic medium releasing carbon dioxide and calcium ions. The calcium ions interact with the anionic polymer (sodium alginate) in the formulation causing instantaneous Gelation and provide a gel barrier that restricts drug release. Formulations containing calcium carbonate alone produce stiffer floating in situ gels than those containing CaCO3. This is due to the internal ionotropic Gelation effect of calcium on sodium alginate.
Table 06: Invitro graded gel response data
|
Formulation Code |
Graded Gel Response |
|
F1 |
+ |
|
F2 |
++ |
|
F3 |
++ |
|
F4 |
+++ |
|
F5 |
++ |
|
F6 |
++ |
|
F7 |
++ |
|
F8 |
+++ |
|
F9 |
++ |
|
F10 |
++ |
|
F11 |
+++ |
|
F12 |
+++ |
Viscosity studies
The formulation should have an optimum viscosity that will allow ease of administration and swallowing as a liquid and produces satisfactory gel strength for use as a delivery vehicle. The formulations showed a viscosity order of Karaya gum <Ethyl cellulose<Carbopol < HPMC K100M. In addition to the influence of the type of viscosity enhancing polymer added, it was observed that increasing the concentration of the viscosity enhancing polymer in the formulation simultaneously increased the viscosity for all polymer types studied.
Table 07: Viscosity data of Oral Insitu Gels of Eplerenone
|
Formulation Code |
Viscosity(cps) |
|
F1 |
267 |
|
F2 |
287 |
|
F3 |
312 |
|
F4 |
245 |
|
F5 |
256 |
|
F6 |
274 |
|
F7 |
289 |
|
F8 |
377 |
|
F9 |
386 |
|
F10 |
394 |
|
F11 |
407 |
|
F12 |
422 |
In vitro floating study
The formulated floating in situ gelling system of Eplerenone employed CaCO3as a gas-generating agent. The in vitro floating test revealed the ability of all formulae to maintain buoyant for more than 12 h.
Table 08: Invitro floating Studies
|
Formulation code |
Total floating Time (hrs) |
|
F1 |
? 8 |
|
F2 |
? 9 |
|
F3 |
? 11 |
|
F4 |
? 11 |
|
F5 |
? 8 |
|
F6 |
?10 |
|
F7 |
?12 |
|
F8 |
?12 |
|
F9 |
?9 |
|
F10 |
?11 |
|
F11 |
?12 |
|
F12 |
?12 |
In vitro drug release study
The in vitro release study of Eplerenone from all formulations in 0.1N HCl was conducted for a period of 12 hours.
Table 09: In vitro drug release of Eplerenone floating insitu gel F1-F6
|
Time (hrs) |
F1 |
F2 |
F3 |
F4 |
F5 |
F6 |
|
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
1 |
23.83 |
22.42 |
17.42 |
26.72 |
20.37 |
19.46 |
|
2 |
34.85 |
34.09 |
2672 |
34.42 |
29.48 |
27.08 |
|
3 |
45.95 |
46.46 |
35.96 |
42.15 |
37.71 |
36.08 |
|
4 |
58.85 |
59.72 |
46.82 |
50.82 |
47.95 |
45.16 |
|
5 |
72.05 |
70.08 |
57.13 |
58.18 |
59.31 |
54.05 |
|
6 |
85.92 |
82.23 |
68.16 |
66.56 |
71.31 |
65.82 |
|
7 |
96.16 |
77.82 |
74.32 |
83.63 |
76.38 |
|
|
8 |
88.13 |
82.73 |
95.62 |
87.07 |
||
|
9 |
97.06 |
90.48 |
96.13 |
|||
|
10 |
98.35 |
|||||
|
11 |
||||||
|
12 |
Table 10: In vitro drug release of Eplerenone floating insitu gel F7-F12
|
Time (hrs) |
F7 |
F8 |
F9 |
F10 |
F11 |
F12 |
|
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
1 |
16.18 |
13.45 |
20.08 |
18.05 |
14.46 |
10.05 |
|
2 |
23.75 |
21.53 |
30.46 |
27.43 |
25.28 |
16.59 |
|
3 |
34.09 |
27.41 |
41.06 |
36.98 |
33.72 |
24.49 |
|
4 |
44.16 |
34.08 |
50.08 |
46.65 |
41.18 |
31.15 |
|
5 |
53.08 |
40.16 |
63.79 |
56.58 |
50.02 |
37.75 |
|
6 |
61.63 |
48.09 |
77.86 |
68.13 |
57.95 |
46.36 |
|
7 |
69.42 |
55.13 |
95.19 |
81.13 |
65.13 |
56.12 |
|
8 |
75.98 |
61.31 |
95.67 |
74.05 |
67.43 |
|
|
9 |
83.55 |
69.06 |
|
85.46 |
78.18 |
|
|
10 |
90.55 |
78.43 |
|
96.42 |
88.02 |
|
|
11 |
97.74 |
88.14 |
|
98.06 |
||
|
12 |
99.54 |
Fig 07: In-vitro dissolution profile of F1-F12
Fig 08: In-vitro dissolution profile of F1-F4
Fig 09: In-vitro dissolution profile of F5-F8
Fig 10: Invitro dissolution profile of F9-F12
From the in vitro drug release studies of Eplerenone oral insitu gels using different polymer ratios. Among the all 12 trails F1-F4 trails were formulated using Ethyl cellulose in three different ratios the drug release time was increased with increase in the polymer concentration. F1 formulation 85.92% of drug release at the end of 6hours, while F2 formulation shows 96.16% of drug release at the end of 7hours, while F3 formulation shows 97.06% of drug release at the end of 9hours, whereas F4 formulation shows 98.73% of drug release at the end of 10hours Among all the three formulations cant sustained the drug release for 12hours. So further formulations were prepared using Carbopol. Then F5-F8 trails were formulated using Carbopol in different ratios. F5 formulation shows 95.62% of drug release at the end of 8hours, while F6 formulation shows 96.13% of drug release at the end of 9hours, while F7 formulation shows 97.74% of drug release at the end of 11hours, whereasF8 formulation shows 99.54% of drug release at the end of 12hours. Then F9-F12 trails were formulated using HPMC K4M in different ratios. F9 formulation shows 95.19% of drug release at the end of 7hours, while F10 formulation shows 95.67% of drug release at the end of 8hours, whereas F11 formulation shows 96.42% of drug release at the end of 10hours,whereas F12 formulation shows 98.06% of drug release at the end of 11hours. Among the all 12 formulations, based upon the invitro studies F8 formulation containing higher concentration of Carbopolchoosen as optimized formulation, and has higher viscosity nature the formulation with higher concentration of Carbopol maintains sustained drug release. So the drug release kinetics were performed for the F8 formulation.
Drug release kinetic studies
Zero order release kinetics:F8
Fig 11: Zero order release graph for F8
First order release kinetics: F8
Fig12: First order release graph for F8
Higuchi release plot
Fig 13: Higuchi release graph for F8
Peppas release plot
14: Peppas release graph for F8
Table 11: Drug Release Kinetics of Eplerenone Oral Insitu Gels
|
R2 values |
n values |
||||
|
Formulation |
Zero order |
First order |
Higuchi |
Korsmeyer - Peppas |
Korsmeyer- Peppas (n) |
|
F12 |
0.993 |
0.598 |
0.920 |
0.764 |
1.123 |
The invitro dissolution data for best formulation F8were fitted in different kinetic models i.e, zero order, first order, Higuchi and korsemeyer-peppas equation. Optimized formulation F8 shows R2 value 0.993. As its value nearer to the ‘1’ it is conformed as it follows the Zero order release. The mechanism of drug release is further confirmed by the korsmeyer and peppas plot, if n = 0.45 it is called Case I or Fickian diffusion, 0.45 < n < 0.89 is for anomalous behavior or non-Fickian transport, n = 0.89 for case II transport and n > 0.89 for Super case II transport. The ‘n’ value is 1.123 for the optimised formulation (F8) i.e., n value indicates super case II transport mechanism. The release kinetics for the optimized formula are shown in table.11
Summary and conclusion
Eplerenone oral in-situ gelling systems were prepared by using polymers like HPMC K4M, Carbopol,Ethyl cellulose, Sodium citrate, Calcium carbonate and Sodium alginate. Total of twelve (F1 to F12) formulations were prepared and F12 containing HPMCK4M was found to be the best formulation. Drug and polymers was subjected for compatibility study using FTIR studies, which revealed that there was no interaction between drug and polymers. The prepared formulations were evaluated for drug content, floating lag time, total floating time, viscosity, gelling nature, visual appearance & invitro release studies were also performed. The invitro release studies of all the formulations among them F12 formulation containing HPMCK4M shows drug release of 97.34% by the end of 12hrs. The release kinetics of the optimized formulation was best fitted into Higuchi model (R2 =0.920) and showed zero order (R2 =0.993) drug release with super case IItransport mechanism. From the above experimental results it can be concluded that, Eplerenone was chosen as the model candidate for development of oral insitu gel, since they possesses near ideal characteristics that these drugs must have formulating sustained drug delivery system. The results of study demonstrate that HPMC K4M was suitable to develop sustained release oral insitu gels.
References