Development and Evaluation of Telmisartan Pulsatile Drug Delivery by using Response Surface Methodology

 

Indrajeet S. Patil*, Omkar A. Patil, Girish Chandra R. Mandake, Manoj M. Nitalikar

Department of Pharmaceutics, Rajarambapu College of Pharmacy, Kasegaon-415404, Dist-Sangli, Maharashtra, India.

 

ABSTRACT:

The aim of present study was to develop, evaluate and optimize the pulsincap formulation on the principle based on the pulsatile drug delivery system using Telmisartan drug. Telmisartan is mainly used for treatment of high blood pressure, congestive heart failure, and to increase the chances of living longer after a heart attack. It is an angiotensin II receptor antagonist that is selective for the type I angiotensin receptor. Formalin treatment has been employed to modify the solubility of gelatin capsules. Quantitative test for formaline residue was carried out. FTIR study shown drug and excipient are compatible with each other. Hydrogel plug of various components are prepared and used in pulsincap formulation. The drug content of the formulated pulsincap was found to be in the range 92.65 to 101%. In vitro drug release study in pH 1.2 buffer was zero percent and capsule was intact for first 2 hrs. F8 formulation batch was selected as best formulation as F8 batch released maximum drug in pH 7.4 phosphate buffer than other formulation batches. In the present work an attempt has been made to develop, evaluate and optimize a time or site specific pulsatile drug delivery system of drug Telmisartan.

 

 

 

INTRODUCTION:

Pulsed or pulsatile drug release is defined as the rapid and transient release of a certain amount of drug molecules within a short time-period immediately after a predetermined off-release period.¹ Thisdelivery systems release the drug rapidly and completely after a lag time, thus provide spatial and temporal delivery and increasing patient compliance, have generated increasing interest during recent years for a number of diseases and therapies.² The system is designed according to Circardian rhythm or biological clock which delivers the drug at the right time and at the right place and in the right amount thus, increasing patient compliance.

 

In the pulsatile drug delivery system, initially there is no drug release after which there is an immediate or controlled release of the drug.³ In recent years, there is a continuous interest in the development of controlled drug release systems to achieve the optimal therapeutic effect of drugs. This is based on the increasing awareness of the importance of circadian rhythms with respect to physiology, disease state and drug action which has given rise to the related fields of chronotherapeutics and chronopharmacology.⁴

 

Pulsincap system comprises of a water insoluble capsule body, soluble cap and hydrogel plug. When this capsule comes in contact with the dissolution fluid, it dissolves and after a lag time, the plug gets pushed itself outside the capsule and rapidly releases the drug. The length of the plug and its point of insertion into the capsule controls the lag time.⁵

 

The capsule bodies of size 0 were treated with formaldehyde vapors to make capsule body water insoluble. The amino group in the gelatin molecular chain could react with an aldehyde group of formaldehyde by a Schiff’s base condensation reaction to produce a water insoluble body. Caps were left untreated. When the capsule comes in contact with dissolution media, the cap gets solubilized and the hydrogel plug comes in contact with dissolution media and it gets hydrated and starts to swell and after ejection of the plug from the body, the drug release is facilitated.⁶

 

Telmisartan is used to treat high blood pressure.  It is well absorbed after oral administration and the bioavailability of about 50%and mean peak concentration of Telmisartan is reached in 0.5-1 hour after dosing.  It minimizes the risk of heart attack and stroke. It works by blocking the action of certain natural substance that tighten the blood vessels allowing the blood to flow smoothly and heart to pump efficiently.⁷

 

The main objective of this study was to design, formulate and optimize a pulsatile drug delivery system. For treatment of hypertension central composite design has been commonly used for designing and optimizing different pharmaceutical formulations and processes.

 

MATERIALS AND METHOD:

Materials:

Telmisartan was obtained as gift sample from Lupin Pharmaceuticals (Pune) and HPMC K₄m, Ethyl Cellulose, Poly Vinyl Pyrolidone supplied by Research- Lab Fine Chem Industries (Mumbai). All the ingredients used in research work are analytical grade.

 

Experimental Design:

A central composite design was employed containing two factors evaluated at three levels with α=1 was employed as per the standard protocol based on prefromulation and the experimental trials were performed at all 9 possible combinations. The studied factors (independent variables) were amount of polymer HPMC (X₁), and Ethyl cellulose (X₂). While drug release (DR) at 4 h (Y₁), drug release (DR) at 8 h (Y₂), drug release (DR) at 12 h (Y₃) were used as dependent (responses). Formulation table for pulsincp is given in (Table 1). The process variables (factors) and levels with experimental values are reported in (Table 2)

 

Table 1: 3² Full Factorial Experimental Design Layout for Telmisartan Pulsincap

	Factor 1	Factor 2
Run	A:HPMC	B:Ethyl Cellulose
	mg	mg
1	0	-1
2	-	0
3	0	1
4	1	1
5	1	0
6	-1	1
7	0	0
8	-1	-1
9	1	-1

 

Table 2: Variables levels with experimental values

Sr. No.	Independent Variables	Levels
		-1	0	+1
1	HPMC amount(mg) X1	40	60	80
2	Ethyl Cellulose amount(mg) X2	30	45	60

 

Drug –Characterization:

UV Spectroscopy:

Calibration curve of Telmisartan was plotted in water, and buffer of pH 1.2, 7.4 and 6.8 with different concentration (1, 2, 3, 4, 5 μg/mL). The absorbance of the solution was taken at wavelength 296 nm against the blank solution using UV spectrophotometer.

 

(Drug excipient interaction study) Fourier Transform Infrared (FT-IR) Spectroscopy:

Infrared spectroscopy was used to predict possible interaction between drug and excipients using a FTIR spectrometer (Jasco 4600) at 4000-650cm -1.⁸

 

Preparation of Cross-Linked Gelatin Capsules:

Formalin treatment was employed to modify the solubility of gelatin capsules. Exposure to formalin vapors resulted in an unpredictable decrease in solubility of gelatin owing to the cross-linkage of the amino group in the gelatin molecular chain aldehyde group of formaldehyde by Schiff’s base condensation.^9,10

 

Method:

Hard gelatin capsules of size 0 were taken. Bodies were separated from cap. 25 mL of 15% (v/v) formaldehyde was taken into desiccators and a pinch of potassium permanganate was added to it, to generate vapours of formalin. The wire mesh containing the empty bodies of capsule was then exposed to formaldehyde vapours. The desiccatorswas tightly closed. The caps were not exposed leaving them water-soluble. The reaction was carried out for 12 hrs after which the bodies were removed and dried at 50⁰C for 30 min to ensure completion of reaction between gelatin and formaldehyde vapours. The bodies were then dried at room temperature to ensure removal of residual formaldehyde. These capsule bodies were capped with untreated caps and stored in a polythene bag.¹¹

 

Tests for Formaldehyde Treated Empty Capsules:

Various physical tests include visual defect, identification attributes namely dimensions, solubility studies of treated capsules, and chemical test were carried out simultaneously for formaldehyde treated and untreated capsules. The length and diameter of the capsules were measured before and after formaldehyde treatment, using digital Vernier calliper. Variations in dimensions between formaldehyde, treated and untreated capsules were studied.

 

Solubility study of treated capsules:

For the solubility study, the treated capsule bodies were exposed to 15% formaldehyde solution in varying time intervals. Then formaldehyde exposed capsule bodies were dried in hot air oven. The solubility of bodies was tested in 0.1N HCl. The time at which the capsule dissolves or forms a soft fluffy mass was noted.¹²

 

Qualitative test for free formaldehyde:

Formaldehyde treated bodies of about 25 capsules were cut into small pieces and taken into a beaker containing distilled water. It was stirred for 1 hrs with a magnetic stirrer, to solubilize the free formaldehyde. The solution was then filtered into a 50 mL volumetric flask, washed with distilled water and volume was made up to 50 mL with the washings.

 

Method:

To 1mL of sample solution, add 9 mL of water, 1mL of the resulting solution was taken into a test tube and mixed with 4mL of water and 5mL of acetone. The test tube was heated in a water bath at 40^oC and allowed to stand for 40 min. The solution was less intensely colored than a reference solution prepared at the same time and in the same manner using 1mL of standard solution instead of the sample solution. The comparison was made by examining tubes down their vertical axis.¹³

 

Preparation of hydrogel plug:

The pulsincap hydrogel plug was prepared by compressing equal amount of HPMC K4M and lactose using 7mm punches and dies on a rotary tablet press, keeping variation in thickness and hardness values of tablet plug.

 

Characterization of prepared hydrogel plug:

The prepared hydrogel plug evaluation was carried out for hardness, thickness and lag time test. Hydrogel plugs were plugged to capsule bodies containing formulated granules and the cap was closed. The lag time test was conducted in 7.4 pH phosphate buffer for 6 hrs using USP II dissolution testing apparatus and the drug release was observed.¹⁴

 

Preparation of Telmisartangranules:

Telmisartan granules were prepared by wet granulation method. The composition of different formulations used in the study is represented in Table 3. HPMC K100 and ethyl cellulose were sieved (no.60) separately and mixed with Telmisartan. These powders were blended and granulated with PVP K30. Isopropyl alcohol was used as a granulating agent. The wet mass was passed through a mesh and granules were dried at 50⁰C.

Table3: Formulation Table of Telmisartan granules

Sr. no	Run	Factor 1	Factor 2
		HPMC	Ethyl Cellulose
		mg	mg
	1	60	30
	2	40	45
	3	60	60
	4	80	60
	5	80	45
	6	40	60
	7	60	45
	8	40	30
	9	80	30

 

Characterization of Telmisartan granules formulated with HPMC K4M:

The prepared granules were evaluated for different flow properties which comprised angle of repose, bulk density, tapped density, compressibility index, Hausner’s ratio and drug content. The drug content was evaluated by an UV spectrophotometric method based on the measurement of absorbance at 296 nm.¹⁵

 

Formulation of pulsatile (modified pulsincap) drug delivery system:

Preparation of modified pulsincap:

Equivalent to 80 mg of drug, the prepared granules were filled in the capsule bodies and plugged with formulated hydrogel plug. The treated body and the cap of the capsules were sealed by using 5% ethyl cellulose ethanolic solution. The sealed capsules were coated with enteric coating (5% CAP) to reduce variability in gastric emptying time; coating was repeated until an expected weight gain of 8-12% was obtained.¹⁶

 

Evaluation of modified pulsincap:

Weight variation:

10 capsules were selected randomly from each batch and weighed individually for weight variation.

 

Thickness of cellulose acetate phthalate coating:

The thickness of coating cellulose acetate phthalate to capsule was measured with Vernier calliper and expressed in mm.¹⁷

 

In-vitro release profile:

Dissolution studies of Telmisartan pulsincap was carried out by using USP dissolution Type I apparatus (Basket). In order to simulate the pH changes along the GI tract, three dissolution media with phosphate buffer pH 1.2, 7.4, 6.8 were sequentially used. When performing experiments, the pH 1.2 medium was first used for 2h (since the average gastric emptying time is 2hour), then removed and the fresh pH 7.4 phosphate buffer was added.  After 3 hours fresh pH6.8 dissolution medium was added for subsequent hrs. During the experiment 900 mL of the dissolution medium was used each time. Rotation speed was 50rpm and temperature was maintained at 37ºC. 5mL of dissolution media was withdrawn at predetermined time intervals and fresh dissolution media was replaced. The withdrawn samples were analyzed at 296 nm, UV visible spectrophotometer.¹⁸

 

Statistical analysis of the data and optimization:

Various RSM computations for the current optimization study were performed employing Design Expert software (Design Expert trial version 7.0.3 State-Ease Inc, Minneapolis, MN).

 

Polynomial models including interaction and quadratic terms were generated for all the response variables using multiple linear regression analysis (MLRA) approach. The general form of the MLRA model is represented as the following equation:

 

Y = β0+ β1 X1+β2 X2 +β3 X1X2+ β4 X12 + β5 X22 +β6 X1 X22+ β7 X2 X12

 

Here, b0 is the intercept representing the arithmetic average of all quantitative outcomes of 13 runs; b1 to b7 are the coefficients computed from the observed experimental response valuesof Y; and X1 and X2 are the coded levels of the independent variable(s). The terms X1X2 and X2 i (i= 1–2) represent the interaction and quadratic terms, respectively. Statistical validityof the polynomials was established on the basis of ANOVA provision in the Design expert Software. Subsequently, the feasibility and grid searches were performed to locate the composition of optimum formulations Three-dimensional (3D) response surface plots and two dimensional (2-D) contour plots were constructed based on the model polynomial functions using Design Expert software. These plots are useful to study the effects of various factors on the response at one time and predict the responses of dependent variables at the intermediate levels of independent variables.

 

RESULTS AND DISCUSSION:

Drug Characterization:

UV Spectroscopy:

From calibration curve of Telmisartan, UV absorption maximum of drug was found at 296 nm. As per calibration curve, the correlation coefficient was found to be 0.999 (pH 1.2), 0.999 (pH 7.4) and 0.997 (pH 6.8). Calibration curve obeyed Beer's law in the range of 1-5 μg/mL.

 

FT-IR spectroscopy:

The drug-excipients compatibility was assessed by comparing IR spectra of the drug, and drug-excipient mixture. From the interpretation of spectra it was found that there was no worth change in the wave numbers of the drug and drug-excipients combination. Hence, the drug and excipients were found to be compatible with each other. (Figure 1 and 2)

 

 

Fig.1: FTIR for pure Telmisartan

 

 

Fig. 2: FTIR for drug-excipient mixture

 

Evaluation of Telmisartan granules:

The results of evaluation of the prepared granules are highlighted in (Table 4). All the formulation showed good angle of repose, flow property, Hausner’s ratio and Cars index.

Table 4: Evaluation of Telmisartan granules

Batch No.	Bulk density (g/cm3)	Tapped density (g/cm3)	Hausner’s ratio	Carr’s index   (%)	Angle of repose	%Drug content
F1	0.403±0.002	0.468±0.005	1.16±0.004	14.31±0.003	250.18±0.04	96±0.002
F2	0.343±0.001	0.402±0.005	1.17±0.005	15.17±0.002	210.23±0.03	95±0.0036
F3	0.434±0.005	0.519±0.001	1.18±0.003	15.60±0.005	270.81±0.003	94±0.0013
F4	0.392±0.001	0.465±0.001	1.16±0.005	14.40±0.005	260.95±0.01	95±0.0018
F5	0.314±0.003	0.363±0.005	1.13±0.005	12.12±0.005	260.21±0.01	94±0.0034
F6	0.328±0.001	0.463±0.002	1.14±0.002	15.13±0.002	250.35±0.02	96±0.004
F7	0.368±0.001	0.457±0.001	1.16±0.005	13.27±0.003	240.85±0.04	93±0.0057
F8	0.376±0.002	0.474±0.005	1.17±0.003	14.57±0.004	260.89±0.01	95±0.0065
F9	0.356±0.001	0.460±0.004	1.13±0.005	15.67±0.005	230.56±0.04	95±0.0028

All values are expressed as mean ±SD (n=3).

 

Table 5: Evaluation of treated capsule

Sr.no.	Initial Length of Capsule (mm)	Average Length after formaldehyde treatment (mm)	Initial Diameter of Capsule (mm)	Average Diameter after formaldehyde treatment (mm)
1	19.69	19.69±0.02	6.81	6.82±0.009

 

Evaluation of hydrogel plug:

The formulated hydrogel plugs were evaluated for thickness, hardness and lag time. It was found that 90 mg plug showed 2 hrs lag time and 100 mg plug exhibited 3 hrs lag time. Thus, 100 mg plug was optimized.

 

Evaluation of formulation treated empty capsules:

The evaluation of treated empty capsule (cap and body) was carried out by length and diameter of capsules. The observations are recorded in Table 5.

 

Solubility study for the treated capsules:

When solubility studies were carried for capsule in 0.1 N HCl for 24 hrs, it was observed that for normal capsules, both cap and body dissolved within 15 minutes, whereas for formaldehyde treated capsules, only the cap got dissolved within 15minutes and the remaining body of capsule remained intact for about 24 hrs. Thus, the present work concluded that 8 hrs formaldehyde treatment is sufficient to sustain the release for 18hrs and found that the capsule maintained the physical stability during the dissolution process.

 

Quantitative test for free formaldehyde:

The formaldehyde treated capsules were tested for the presence of free formaldehyde. The sample solution was not more intensely colored than the standard solution inferring that less than 20μg free formaldehyde is present in 25 capsule.

 

Weight variation and thickness of coating:

The capsules filled with granules pass the weight variation test as their weights were found within the specified limits and the thickness of the CAP coating was measured by Vernier calliper which ranged from 0.053-0.070 mm.

 

In-vitro release studies:

In vitro dissolution test for capsules was performed in dissolution media of pH 1.2 and 6.8. The formulations F1 to F9 showed more than 70% drug release (Table 6). Batch F8 exhibited more than 90% drug release.During the dissolution studies, it was observed that, the enteric coat of the cellulose acetate phthalate was intact in pH 1.2, but dissolved in intestinal pH, leaving the soluble cap of capsule, which also got dissolved in pH 7.4 phosphate buffer. Thus, from % drug release studies of various formulation batches, F8 batch was selected as best formulation as it achieved maximum drug release in pH 7.4 phosphate buffer as compared to other formulation batches. The drug release from the formulation was observed to be decreased with an increase in the amount of polymer added in each formulation.(Figure 3 and 4)

 

Table 6: In-vitro Dissolution studies

Sr.no.	Hrs.	Average % Drug release
		F1	F2	F3	F4	F5	F6	F7	F8	F9
1	1	0	0	0	0	0	0	0	0	0
2	2	0	0	0	0	0	0	0	0	0
3	3	9	9.08	9.22	8.50	9.31	9.02	9.27	9.90	9.30
4	4	15.78	16.2	13.35	13.22	12.23	15.6	15.56	18.24	16.96
5	5	22.70	23.67	22.89	24.2	25.16	23.84	24.63	25.30	26.22
6	6	31.6	32.45	32.78	34.26	33.18	40	35.68	37	36.25
7	7	41.58	40	45.26	47.54	45.48	52.85	46.32	52.41	47.28
8	8	62.46	60.62	63.65	60.14	59.31	63.69	62.6	63.12	61.14
9	9	71.25	67.5	70.6	67.25	65.1	70.87	70.54	70.47	72.20
10	10	79.9	74.58	78.45	73.87	71.64	75.8	74.7	76.22	80.52
11	11	85.33	82.27	81.26	82.25	80.33	81.98	82.7	85.2	86.3
12	12	91.56	90.61	87.34	90.42	85.56	90.54	90	92.65	91.54

 

 

Fig.3: In-vitroDissolution studies F1to F5

 

 

Fig.4:In-vitroDissolution studies F6 to F9

 

Effect of formulation variables on drug release at 4 hrs:

Drug release play important role in all formulation as we know the drug release of dosage form is depend up on amount of polymer used in formulation. Amount of polymer used in formulation having significant effect on drug release. In formulations, F1–F9 drug release was in the range of 15.78 to 16.96 at 4 hrs, maximum drug release 18.24 was shown by formulation F8, where as minimum drug release was shown by13.22 was shown by formulation F4. The effect of the variables on the drug release in formulations F1–F9 are shown in below (Figure 5) and (Figure 6) respectively

 

Y₁ = 15 – 1.17x₁ -1.22X₂                                               (1)

 

All the polynomial equations were found to be statistically significant (𝑃<0.0010), as determined using ANOVA, as per the provision of Design Expert software. The combined effect of concentration of HPMC and Ethyl cellulose on drug release at 4 hrs was shown in counter plot and in 3D response surface plot. In above equation X₁ Bears / having negative sign and X₂ also Bears / having negative sign which shows that decreased / at lower concentration of HPMC and Ethyl cellulose is required for get optimum drug release at 4hrs. From the plots and polynomial equation it can concluded that both factor HPMC (X₁) and Ethyl cellulose(X₂) having significant effect on drug release at 4 hrs.

Table 7: ANOVA for response surface quadratic model for drug release at 4 hrsAnalysis of variance table.

Parameters	Sum of Squares	df	Mean Square	F value	p-value Prob > F	Remark
Drug release at 4 hrs(Quadratic model)	22.79	2	11.40	14.91	0.0010	significant
X1	10.87	1	10.87	14.22	0.0037
X2	11.92	1	11.92	15.60	0.0027
Residual	7.64	10	0.76
Lack of Fit	7.64	6	1.27
Pure Error	0.000	4	0.000
Cor Total	30.43	12

 

 

Fig. 5: Contour plot (A) showing the effect of the amount of polymer HPMC and Ethyl Cellulose on drug release at 4 hrs from Telmisartan pulsincap

 

 

Fig. 6: Response surface plot (A) showing the effect of the amount of polymer HPMC and Ethyl cellulose on drug release at 4 hrs from Telmisartan pulsingcap

 

Effect of formulation variables on drug release at 8 hrs:

Drug release play important role in all formulation as we know the drug release of dosage form is depend up on amount of polymer used in formulation. Amount of polymer used in formulation having significant effect on drug release. In formulations, F1–F9 drug release was in the range of 59.31 to 63.69at 8 hrs, maximum drug release 63.69 was shown by formulation F6, where as minimum drug release was shown by59.31was shown by formulation F5. The effect of the variables on the drug release in formulations F1–F9 are shown in below (Figure 7) and (Figure 8) respectively

 

Y₂ = 62.60 – 0.87X₁ + 0.11X₂ – 0.49X₁X₂ - 1016 X₁ + 0.38X₂ (2)

 

All the polynomial equations were found to be statistically significant (𝑃<0.0010), as determined using ANOVA, as per the provision of Design Expert software. The combined effect of concentration of HPMC and Ethyl cellulose on drug release at 8 hrs was shown in counter plot and in 3D response surface plot. In above equation X₁ Bears / having negative sign and X₂ also Bears / having negative sign which shows that decreased / at lower concentration of HPMC and Ethyl cellulose is required for get optimum drug release at 4hrs. From the plots and polynomial equation it can concluded that both factor HPMC (X₁) and Ethyl cellulose(X₂) having significant effect on drug release at 8 hrs.

 

Table 8: ANOVA for response surface quadratic model for Drug release at 8 hrs Analysis of variance table [Partial sum of squares - Type III].

Parameters	Sum of Squares	df	Mean Square	F Value	p-value Prob > F	Remark
Drug release at 8 hrs (Quadraticmodel)	18.59	5	3.72	9.03	0.0058	Significant
X1	6.09	1	6.09	14.80	0.0063
X2	0.091	1	0.091	0.22	0.6527
X1X2	0.97	1	0.97	2.36	0.1687
X12	9.43	1	9.43	22.91	0.0020
X22	1.01	1	1.01	2.45	0.1617
Residual	2.88	7	0.41
Lack of Fit	2.88	3	0.96
Pure Error	0.000	4	0.000
Cor Total	21.48	12

 

 

Fig. 7: Contour plot showing the effect of the amount of polymer HPMC and Ethyl Cellulose on drug release at 8 hrs from Telmisartan pulsincap.

 

 

Fig. 8:Response surface plot (A) showing the effect of the amount of polymer HPMC and Ethyl cellulose on drug release at 8hrs from Telmisartan pulsincap

 

Effect of formulation variables on drug release at 12 hrs:

Drug release play important role in all formulation as we know the drug release of dosage form is depend up on amount of polymer used in formulation. Amount of polymer used in formulation having significant effect on drug release. In formulations, F1–F9 drug release was in the range of 85.56 to 92.65 at 12 hrs, maximum drug release 92.65 was shown by formulation F8, where as minimum drug release was shown by85.65 was shown by formulation F5. The effect of the variables on the drug release in formulations F1–F9 are shown in below (Figure 9) and (Figure 10) respectively

 

Y₃ = 90.02 – 1.05X₁ – 1.15X₂ (3)

 

All the polynomial equations were found to be statistically significant (𝑃<0.0010), as determined using ANOVA, as per the provision of Design Expert software. The combined effect of concentration of HPMC and Ethyl cellulose on drug release at 8 hrs was shown in counter plot and in 3D response surface plot. In above equation X₁ Bears / having negative sign and X₂ also Bears/ having negative sign which shows that decreased/ at lower concentration of HPMC and Ethyl cellulose is required for get optimum drug release at 4h. From the plots and polynomial equation.

 

Table 9: ANOVA for response surface quadratic model for drug release at12hrs Analysis of variance table [Partial sum of squares-Type III].

Parameters	Sum ofSquares	df	MeanSquare	F Value	p-value Prob > F	Remark
Drug release at 12hrs (Quadraticmodel)	19.34	2	9.67	4.81	0.0345	significant
X1	8.76	1	8.76	4.35	0.0635
X2	10.58	1	10.58	5.26	0.0448
Residual	20.12	10	2.01
Lack of Fit	20.12	6	3.35
Pure Error	0.000	4	0.000
Cor Total	39.45	12

 

 

Fig. 9: Contour plot showing the effect of the amount of polymer HPMC and Ethyl Cellulose on drug release at 12 hrs from Telmisartan pulsincap.

 

 

Fig.10: Response surface plot (A) showing the effect of the amount of polymer HPMC and Ethyl cellulose on drug release at 12hrs from Telmisartan pulsincap.

Optimization criteria for Telmisartan pulsincap:

This was the most important part of response surface methodology. The formulation of the drug which released the drug in controlled and complete manner was selected for optimum formulation. The criteria for optimum formulation ofTelmisartan pulsincap are given in (Table 10).

 

Table 10.Release kinetics of optimum formulation

Release property	Range
Release at 4 h	15 – 18 %
Release at 8 h	60 – 63 %
Release at 12 h	90 – 92 %

 

Optimization of Telmisartan pulsincap:

Formulation F8 was select as optimized formulation which fit in given criteria for optimization of formulation. Formulation F8 release the drug in controlled and complete manner.

 

CONCLUSION:

Novel pulsincap formulations were successfully developed by filling of granules in a capsule body. The capsule body containing granules after plugging with a polymer and sealed with a cap was completely enteric coated with 5% w/w cellulose acetate phthalate. Formulation F-8was considered as the best formulations as they shown a complete lag time24of hrs and released 92.65% at the end of 12 hrs respectively. Thus, pulsincap formulations will prove to be suitable for optimum colonic delivery of Telmisartan in the treatment of hypertension as per chronotherapy.

 

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Received on 05.02.2018       Accepted on 28.04.2018     

© Asian Pharma Press All Right Reserved

Asian J. Pharm. Res. 2018; 8(4): 205-214.

DOI: 10.5958/2231-5691.2018.00035.7