Formulation and Evaluation of Israpidine Extended Release Matrix Tablets

Praveen Kumar Uppala*, K. Atchuta Kumar, Murali Krishna, U. Upendra Rao

Bhaskara Institute of Pharmacy, Affiliated to Andhra University, Vizianagaram

*Corresponding Author E-mail: praveen.chintu32@gmail.com

ABSTRACT:

The purpose of this study was to formulate and evaluate an efficient Isradipine extended release matrix tablets designed to provide 24 hours drug release profile using varying proportion of hydrophilic polymers viz; Lactose monohydrate and HEC as matrix-forming material. Prepared matrix tablets showed satisfactory physicochemical properties where drug content was 98.24% to 101.06 %, thickness was 3.33 mm to 3.55 mm, hardness was 7.52±0.171 to 8.94±0.285 kg/cm2 , friability was less than 1% and % weight variation was within the standard pharmacopoeial limits of ±7.5% of the weight. Mathematical analysis of the release kinetics of the optimized formulation (F15) was best fitted in zero order kinetics (R2 = 0.9743). The dissolution profiles of formulation F15 and innovator product in multi media were compared in pH 4.5 acetate buffer, pH 6.8 phosphate buffer, 0.1N HCl respectively. The stability data reveals that the F15 showed a negligible change in drug content after storage in various conditions for two months according to ICH guidelines.

KEYWORDS: Isradipine, Matrix tablets, Lactose monohydrate, HEC, extended release

INTRODUCTION:

To achieve and maintain the drug concentration in the body with in the therapeutic range required for a medication, it is often necessary to take this type of drug-delivery system several times a day A number of technical advancements have been recently made in developing new technologies for day delivery the rate of drug delivery, sustaining the duration of the therapeutic action and/or targeting the delivery of drug to a tissue. These advancements have already led to the development of several novel drug delivery systems that could provide one/more of the following.

1) Controlled administration of a therapeutic dose at a desirable delivery state.

2) Maintenance of drug concentration with in an optimal therapeutic range for prolonged

duration of treatment.

3) Maximization of efficacy-dose relationship.

4) Reduction of adverse side effects.

5) Maximization of the needs for fragment dose intake and patient compliance.

Matrix tablets:

These are the simplest and least expensive systems for controlled drug delivery. Their processing is reproducible and is similar to that conventional system. The polymer or other carrier is homogeneously mixed with drug.

MATERIALS AND EQUIPMENT

Table: 1 List of Materials

S.No	Name of the ingredients	Category	Monograph ref.
1	ATENOLOL	Drug	USP
2	Lactosemonohydrate (Lactochem)	Diluent	USP/NF,EP,JP
3		Rate retarding polymer	USP/NF,EP,JP
4	Methocel E4M	Rate retarding polymer	USP/NF,EP,JP
6.	Methocel E50	Binder	USP/NF,EP,JP
6.	Hypermellose (5 cps)	Binder	USP/NF,EP,JP
7.	Hydroxy propyl cellulose(HPC –LF)	Binder	USP/NF,EP,JP
8.	Poly ethylene glycol (PEG -400)	Plasticiser	USP/NF,EP,JP
9.	Isopropyl alchol	Solvent	IH
10.	Dichloro methane	Solvent	IH
11.	Purified water	Vehicle
12	Aerosil	Glidant	USP/NF,EP,JP
13	Magnesium stearate	lubicant	USP

Formulation Development Formulations with Drug in dry mix

Table: 2 Compilation of Isradipine extended release matrix Tablet

s.no	Contents	F1	F2	F3	F4	F5	F6	F7
(mg/tab)
A. Dry mix
1.	Isradipine	10	10	10	10	10	10	10
2.	DCP	208	208	208	208	168	213	208
3.	HPMC E50	60	60	60	30	100	60	-
4.	HPMC E4M	-	-				15	60
B.BINDER
5.	Surelease	10				-	-	-
6.	Water	q.s	q.s	q.s	q.s	q.s	q.s	q.s
C.LUBRICATION
7.	HPMC E4M CR	-	15	30	30	-	-	-
8.	Magnesium stearate	2	2	2	2	2	2	2
Average weight(mg)		290	295	310	300	280	300	300
Bulk density(g/mL) premix		0.378	0.367	0.369	0.362	0.351	0.371	0.365
Hardness(kp)		5-7	5-7	5-7	5-7	10-11	5-7	5-7
Thickness(mm)		3.8-4.2	3.8-4.2	3.8-4.2	3.8-4.2	5-7	3.8-4.2	3.8-4.2
Disso results (24hr avg=6)(%)		78	44	43	33	80	77	57

F=Formulation Batches

In F1: in the first trial F1,10 mg of isradipine,208 mg of DCP,60 mg of HPMC E50 were co sifted and about 1:1 dilution of surelease:water was used as binder and granulated , lubricated with magnesium stearate and compressed.

In F2: same formula as that of F1 but surelease is omitted in granulation .Granules were separated into 2 parts and for 1 part 15 mg HPMC E4 M was added ,lubricated , compressed.

In F3: in formulation F3, another part of granulation is taken to that 30 mg of HPMC E 4M per tablet was added ,lubricated and compressed.

In F4: in formulation F4 ,in dry mix quantity of HPMC E 50 was reduced to half (30 mg/tablet ) and granulated with water , to that 30 mg of HPMC E 4M per tablet was added ,lubricated and compressed.

In F5: in formulation F5,in dry mix quantity of HPMC E50 Was increased to 100mg/tb ,DCP was reduced to 168 mg /tab ,granulated ,lubricated and compressed with higher hardness.

In F6: in formulation F6 ,in dry mix HPMC E 50 60mg ,HPMC E 4 M 15 mg/tb was included ,granulated, lubricated and compressed.

In F7: in formulation F7, same as that of F6 but HPMC E 4 M quantity was increased to 60 mg /tb in dry mix. granulated, lubricated and compressed.

Strategy-2

Table: 3 Compilation of strategy 2

S.No	contents	F8(mg/tb)	F9(mg/tb)
DRY MIX
1.	DCP	50	50
2.	HPMC E 50	25	25
DRUG SOLUTION
3.	Isradipine	10	10
4.	DCM	q.s	q.s
5.	HPMC 5 cps	4	4
6.	IPA	q.s	q.s
LUBRICATION
7.	Dicalcium phosphate (di tab)	-	60
8.	Magnesium stearate	1	1
Average weight (mg)		90	90
Bulk density (g/mL)pre mix		0.361	0.364
Hardness (Kp)		5-5.8	7.5-8.5
Thickness(mm)		3.6-3.11	3.6-3.8

IN F8: in this formulation 50mg/tb DCP ,25 mg/tb HPMC E 50 were co sifted and loaded in FBP and drug solution was sprayed ,granulated ,dried , lubricated with magnesium stearate and compressed.

IN F9: Same as that of F8 to this extra granular 60mg/tb DITAB was added ,lubricated ,compressed.

Strategy-2

Table: 4 Compilation of strategy 3

S.no	Contents	F10	F11	F12	F13	F14	F15
Dry mix
1.	Lactose mono hydrate	49	49	49	74	64	60
2.	HEC	25	25	25	15	15	20
Drug solution
3.	Isradipine	10	10	10	10	10	10
4.	HPMC 5 cps	5	5	5	5	5	5
5.	IPA	q.s	q.s	q.s	q.s	q.s	q.s
6.	DCM	q.s	q.s	q.s	q.s	q.s	q.s
Binder solution
7.	HPC- LF	8	8	8	8	8	8
8.	PEG-400	1	1	1	1	1	1
9.	Purified water	q.s	q.s	q.s	q.s	q.s	q.s
Lubricants
10.	Lactose monohydrate	-	25	50	-	-	-
11.	Aerosil	1.5	1.5	1.5	1	1	1
12.	Magnesium stearate	1	1	1	1	1	1
Average weight(mg)		100	100	125	150	115	106
Bulk density(g/mL) (premix)		0.360	0.354	0.353	0.357	0.364	0.360
Hardness(Kp)		8-9	8-9	7-9	7-9	7-9	7-9
Thickness(mm)		3.5-3.9	2-2.5	3.8-4.1	4.8-5.0	3-4	3.3-3.5

IN F10: In this formulation,49mg/tab of lactose ,25 mg/tb HEC were co sifted and loaded in FBP and drug solution was sprayed , then binder HPC was sprayed, granulated ,dried , lubricated with magnesium stearate and compressed.

IN F11: Same as that of F8 to this extra granular 25mg/tb LACTOSE was added, lubricated ,compressed.

IN F12: Same as that of F8 to this extra granular 50mg/tb LACTOSE was added ,lubricated ,compressed.

IN F13: In this formulation,74mg/tab of lactose,15 mg/tb HEC were co sifted and loaded in FBP and drug solution was sprayed , then binder HPC was sprayed ,granulated ,dried , lubricated with magnesium stearate and compressed.

IN F14: Same as that of F13 but decreased concentration of LACTOSE was added granulated, lubricated, compressed.

IN F15: Same as that of F14 but decreased concentration of LACTOSE, increased concentration of HEC was added granulated, lubricated, compressed.

Table: 5 Preformulation Studies For API

S.No.	Characteristics	Results
1.	Organoleptic Evaluation	Yellow colored fine crystalline powder odorless
2.	Solubility Analysis	0.091mg/ml in water, 0.037mg/ml in 0.1NHCl, 0.05mg/ml in P^H 4.5 Acetate buffer, 0.06mg/ml in P^H 6.8 Phosphate buffer, 0.427mg/ml in 0.1%LDAO, 0.654mg/ml in 0.2%LDAO
3.	Bulk density	0.39 g/ml
4.	Tap density	0.221g/ml
5.	Compressibility index	41.11%
6.	Hausner’s ratio	1.698
7.	Melting point	168-169⁰C (169.9)-DSC 5⁰C/min

Table : 6 Results of Compatibility study

S. No	Name of the Excipient	Ratio API: Expt	Initial Observation	Final observation		Conclusion
				40°C/75% RH
				2^nd week	4^th week
1	API (Isradipine)	---	yellow	yellow	yellow	Compatible
2	API+ DCP	1 :1	yellow	yellow	yellow	Compatible
3	API + MCC	1 : 1	yellow	yellow	yellow	Compatible
4	API + Lactose monohydrate	1 : 1	yellow	yellow	yellow	Compatible
5	API + Mannitol SD-100	1 : 1	yellow	yellow	yellow	Compatible
6	API + HEC	1 : 1	yellow	yellow	yellow	Compatible
7	API + HPC	1 : 1	yellow	yellow	yellow	Compatible
8	API + HPMC E50	1 : 1	yellow	yellow	yellow	Compatible
9	API + HPMC 5cps	1: 1	yellow	yellow	yellow	Compatible
11	API + Surelease	1:1	yellow	yellow	yellow	Compatible
12	API + PEG-400	1: 1	yellow	yellow	yellow	Compatible
13	API + TEC	1:1	yellow	yellow	yellow	Compatible
14	API + Magnesium stearate	1:0.5	yellow	yellow	yellow	Compatible

Table: 7 Results of Physical Evaluation (tablet)

S. No	Physical parameter	F 1	F 2	F 3	F 4	F 5	F 6	F 7
1	Weight variation	1.65	1.57	1.42	1.54	1.18	1.35	1.44
2	Hardness (Kg/Square inch)	5-7	5-7	5-7	5-7	10-11	5-7	5-7
3	Thickness (mm)	3.8-4.2	3.8-4.2	3.8-4.2	3.8-4.2	5-7	3.8-4.2	3.8-4.2

Table: 7--Cont..

S. No	Physical parameter	F 8	F 9	F 10	F 11	F12	F13	F14	F15
1	Weight variation	1.23	1.48	1.63	1.38	1.24	1.28	1.20	1.20
2	Hardness (Kg/Square inch)	5-6	7-8.5	8-9	7-9	7-9	7-9	7-9	7-9
3	Thickness (mm)	3.94	4.00	2-2.5	3.8-4.1	4.8-5.0	3-4	3-4	3.3-3.5

Table: 8 Results of Chemical Evaluation of tablets

S No

Parameter

F 1

F 2

F 3

F 4

F 5

F 6

Assay

Within the limit

Dissolution study

Not With in the limit

not

With in the limit

not

With in the limit

not

With in the limit

not

With in the limit

not

With in the limit

Table: 8, Cont..

S No

Parameter

F 7

F 8

F 9

F 10

F 11

F 12

Assay

Within the limit

With in the limit

Dissolution study

not

With in the limit

Table: 9 Dissolution profile for Isradipine extended release tablets: ( Reference-DYNACIRC)

S.No	Time(hr)	%Drug Dissolved							% RSD
S.No	Time(hr)	Sample-1	Sample-2	Sample-3	Sample-4	Sample-5	Sample-6	MEAN(Q)	% RSD
1	0	0	0	0	0	0	0	0	0
2	2	13	6	10	5	7	6	8	39
3	4	36	22	31	20	24	23	26	23.7
4	6	55	39	49	39	48	37	45	16.19
5	8	71	53	70	56	68	55	62	13.40
6	10	91	68	88	72	86	68	79	13.48
7	12	100	84	99	89	99	88	93	7.48
8	16	100	100	99	99	101	97	99	1.38
9	24	101	100	99	99	101	97	100	1.52

COMPARATIVE DISSOLUTION PROFILES

For the formulations F1to F7 are not up to mark .So as they are not comparable with the innovator the comparison started from F8.

Table: 10 Dissolution profile of F8

S.No	Time	% Drug Dissolved
S.No	Time	Sample -1	Sample-2	Sample-3	Sample-4	Sample-5	Sample-6	Mean	%RSD
1	0 hr	0	0	0	0	0	0	0	0
2	2 hr	16	18	21	16	16	15	17	12.8
3	4 hr	32	36	40	35	38	37	36	7.59
4	6 hr	47	55	62	60	49	50	53.8	11.5
5	8 hr	65	74	86	85	75	69	75.7	11.1
6	10 hr	91	93	96	95	90	95	93.3	2.6
7	12 hr	96	96	96	95	94	95	95.3	0.9
8	16 hr	96	96	96	95	95	95	95.5	0.6
9	24 hr	97	97	97	97	97	97	97	0

FIGURE 2 Comparative Dissolution Profile of F8 With Reference

Table: 11 Dissolution profile of F9

S.No	Time	% Drug Dissolved
S.No	Time	Sample -1	Sample-2	Sample-3	Sample-4	Sample-5	Sample-6	Mean	%RSD
1	0 hr	0	0	0	0	0	0	0.0	0.0
2	2 hr	13	13	11	7	16	14	12.0	25.83
3	4 hr	31	28	26	18	34	27	27.0	20
4	6 hr	52	42	37	29	49	37	41.0	20.73
5	8 hr	62	53	44	41	57	45	50.0	16.6
6	10 hr	66	59	51	50	62	52	57.0	11.58
7	12 hr	69	62	56	55	65	57	61.0	9.18
8	16 hr	71	67	62	62	70	64	66.0	5.91
9	24 hr	77	73	71	69	76	70	73.0	4.53

FIGURE 3 :Comparative Dissolution Profile of F9 With reference

Table: 12 Dissolution profile of F10

s.no	time	% Drug Dissolved
s.no	time	Sample- 1	Sample- 2	Sample- 3	Sample- 4	Sample- 5	Sample- 6	MEAN	%RSD
1	0	0	0	0	0	0	0	0	0
2	2 hrs	4	5	7	9	5	6	6	29.8
3	4 hrs	11	15	19	17	14	19	15.83	19.73
4	6 hrs	21	26	34	32	29	25	27.83	17.21
5	8 hrs	31	39	50	48	32	40	40	19.68
6	10 hrs	43	52	65	64	56	51	55.2	15.18
7	12 hrs	54	64	77	75	68	64	67	12.52
8	16 hrs	75	79	91	90	76	85	82.6	8.47
9	24 hrs	97	99	104	96	88	90	95.7	6.15

FIGURE 4 :Comparative Dissolution Profile of F10 With reference

Table: 13 Dissolution profile of F11

S.No	time	% Drug Dissolved
S.No	time	Sample- 1	Sample- 2	Sample- 3	Sample- 4	Sample- 5	Sample- 6	MEAN	%RSD
1	0	0	0	0	0	0	0	0	0
2	2 hrs	69	83	47	53	54	63	61.5	21.31
3	4 hrs	86	93	56	56	59	70	70	23.02
4	6 hrs	96	98	66	68	69	82	79.83	18.1
5	8 hrs	97	99	73	76	77	89	85.2	13.33
6	10 hrs	97	98	79	78	78	93	87.2	11.27
7	12 hrs	97	98	84	88	89	94	91.67	6.04
8	16 hrs	97	98	89	92	94	96	94.3	3.58
9	24 hrs	97	98	94	94	96	96	95.83	1.67

FIGURE 5: Comparative Dissolution Profile of F11 With reference

Table: 14 Dissolution profile of F12

S.No	Time	% Drug Dissolved
S.No	Time	Sample -1	Sample-2	Sample-3	Sample-4	Sample-5	Sample-6	Mean	%RSD
1	0 hr	0	0	0	0	0	0	0.0	0.0
2	2 hr	70	89	90	75	82	85	81.8	7.93
3	4 hr	83	98	96	95	87	95	92.3	5.92
4	6 hr	93	99	96	95	96	97	96.0	2
5	8 hr	97	99	97	98	96	97	97.3	1.032
6	10 hr	98	98	96	97	97	97	97.2	0.75
7	12 hr	98	98	97	97	97	97	97.3	0.516
8	16 hr	98	98	97	97	97	97	97.3	0.516
9	24 hr	98	98	97	97	97	97	97.3	0.516

FIGURE 6 Comparative Dissolution Profile of F12 With Reference

Table: 15 Dissolution profile of F13

S.No	Time(hr)	%Drug Dissolved							%RSD
S.No	Time(hr)	Sample-1	Sample-2	Sample-3	Sample-4	Sample-5	Sample-6	MEAN(Q)	%RSD
1	0	0	0	0	0	0	0	0	0
2	2	13	13	14	13	13	10	13	11
3	4	33	34	36	34	34	27	33	9.4
4	6	65	57	58	64	56	57	60	6.62
5	8	90	88	85	89	87	84	87	2.66
6	10	99	95	95	98	99	90	96	3.61
7	12	102	105	105	106	104	102	104	1.61
8	16	104	105	105	106	106	105	105	0.72
9	24	105	106	105	110	106	105	106	1.83

FIGURE 7 Comparative Dissolution Profile of F13 With Reference

Table: 16 Dissolution profile of F14

S.No	Time(Hr)	%Drug Dissolved							%RSD
S.No	Time(Hr)	Sample-1	Sample-2	Sample-3	Sample-4	Sample-5	Sample-6	MEAN(Q)	%RSD
1	0	0	0	0	0	0	0	0	0
2	2	13	15	12	13	11	12	13	11
3	4	37	33	34	32	34	28	33	9.0
4	6	61	57	59	61	63	65	61	4.64
5	8	87	85	82	83	88	90	86	3.57
6	10	95	95	93	98	98	97	96	2.08
7	12	99	100	99	98	100	99	99	0.76
8	16	102	100	100	100	101	103	101	1.25
9	24	105	102	104	102	103	103	103	1.13

FIGURE 8 Comparative Dissolution Profile of F14 With reference

Table: 17 Dissolution profile of F15

S.No	Time(Hr)	%Drug Dissolved							%RSD
S.No	Time(Hr)	Sample-1	Sample-2	Sample-3	Sample-4	Sample-5	Sample-6	MEAN(Q)	%RSD
1	0	0	0	0	0	0	0	0	0
2	2	15	14	14	12	14	15	14	8
3	4	24	23	25	24	26	23	24	4.8
4	6	45	37	44	44	48	39	43	9.50
5	8	62	66	64	64	65	64	64	2.07
6	10	72	77	73	75	74	75	74	2.36
7	12	86	90	86	88	90	91	89	2.45
8	16	91	94	92	95	99	95	94	2.97
9	24	98	99	99	100	100	98	99	0.90

FIGURE 9 Comparative Dissolution Profile of F15 With reference

COMPARATIVE DISSOLUTION PROFILE OF F8 TO F15

S.No	time(hr)	Mean % drug dissolved
		F8	F9	F10	F11	F12	F13	F14	F15
1	0	0	0.0	0	0	0.0	0	0	0
2	2	17	12.0	6	61.5	81.8	13	13	14
3	4	36	27.0	15.83	70	92.3	33	33	24
4	6	53.8	41.0	27.83	79.83	96.0	60	61	43
5	8	75.7	50.0	40	85.2	97.3	87	86	64
6	10	93.3	57.0	55.2	87.2	97.2	96	96	74
7	12	95.3	61.0	67	91.67	97.3	104	99	89
8	16	95.5	66.0	82.6	94.3	97.3	105	101	94
9	24	97	73.0	95.7	95.83	97.3	106	103	99

FIGURE 10 Comparative dissolution profile of Formulation with Innovator

SELECTION OF THE FINAL FORMULA:

Based on f₂ values comparative with reference product final formulation was selected.

Formula	F8	F9	F10	F11	F12	F13	F14	F15
Similarity factor(f₂ )	44	26	30	20	19	36	40	63
Dissimilarity factor(f₁ )	13	26	24	32	34	18	15	5

CALUCULATION OF f1 AND f2 OF F15

DISSOLUTION PROFILE COMPARISION
Time (hrs)	REFERENCE(R)	F12 (T)	/R-T/	/R-T/²	f2 value
0	0	0	0	0	63(f1=5)
2	8	14	-6	36
4	26	24	2	4
6	45	43	2	4
6	62	64	-2	4
10	79	74	5	25
12	93	89	4	16
16	99	94	5	25
24	100	99	1	1
TOTAL	512	501	11	115

COMPARATIVE KINETICS OF F13,F14,F15 WITH REFERENCE PRODUCT

FORMULA	ZERO ORDER		HIGUCHI		PEPPAS
	R²	K₀	R²	K (hr^-1)	R²	n
REFERENCE	0.96	14.4	0.96	14.01	0.899	1.05
F13	0.98	20.8	0.90	14.6	0.738	0.116
F14	0.96	18.4	0.89	14.8	0.65	0.198
F15	0.97	13.25	0.97	13.26	0.94	0.87

‘n’ value for peppas was 0.87 indicating it follows non fickian diffusion

INNOVATOR DISSOLUTION

S.No	time	% drug dissolved
S.No	time	Sample- 1	Sample- 2	Sample- 3	Sample- 4	Sample- 5	Sample- 6	MEAN	%RSD
1	0	0	0	0	0	0	0	0	0
2	2 hrs	4	5	1	3	4	2	3.17	50
3	4 hrs	15	16	12	13	14	13	13.83	10.71
4	6 hrs	22	21	18	17	19	20	19.5	9.5
5	8 hrs	25	23	21	21	22	23	22.5	6.53
6	10 hrs	26	26	26	29	26	25	26.3	5.38
7	12 hrs	32	29	26	27	29	32	29.17	8.62
8	16 hrs	36	33	32	29	32	31	32.17	7.19
9	24 hrs	48	46	43	44	40	40	43.5	7.27

DISSOLUTION OF F15

S.No	time	% drug dissolved
S.No	time	Sample- 1	Sample- 2	Sample- 3	Sample- 4	Sample- 5	Sample- 6	MEAN	%RSD
1	0	0	0	0	0	0	0	0	0
2	2 hrs	11	14	14	12	10	10	11.8	16.4
3	4 hrs	19	18	18	17	15	15	17	9.8
4	6 hrs	23	22	23	22	20	22	22	6.2
5	8 hrs	27	26	26	26	23	23	25.16	6
6	10 hrs	29	37	28	28	26	26	29	13.3
7	12 hrs	31	31	30	31	29	29	30.16	3.3
8	16 hrs	33	33	32	33	32	31	32.33	2.6
9	24 hrs	35	34	34	35	36	34	34.6	2.3

FIGURE 11

DISSOLUTION OF pH 6.8 PHOSPHATE BUFFER INNOVATOR:

S.No	time	% drug dissolved
S.No	time	sample- 1	sample- 2	sample- 3	sample- 4	sample- 5	sample- 6	MEAN	%RSD
1	0	0	0	0	0	0	0	0	0
2	2 hrs	4	5	2	4	4	4	3.83	25
3	4 hrs	16	17	14	17	16	16	16	6.88
4	6 hrs	20	20	19	21	20	20	20	3
5	8 hrs	23	23	23	24	24	22	23.17	3.48
6	10 hrs	26	26	24	27	26	25	25.7	3.85
7	12 hrs	30	26	29	26	30	28	28.7	6.43
8	16 hrs	34	34	32	33	35	33	33.5	2.94
9	24 hrs	34	34	32	33	34	34	33.5	2.35

F15:

S.No	time	% drug dissolved
S.No	time	sample- 1	sample- 2	sample- 3	sample- 4	sample- 5	sample- 6	MEAN	%RSD
1	0	0	0	0	0	0	0	0	0
2	2 hrs	11	9	8	11	12	11	10.3	15.1
3	4 hrs	16	14	14	16	17	17	15.7	8.5
4	6 hrs	22	18	18	20	22	22	20.3	9.8
5	8 hrs	26	22	23	24	26	25	24.3	6.9
6	10 hrs	29	24	26	26	29	29	27.17	8.1
7	12 hrs	31	28	28	29	31	30	29.5	4.6
8	16 hrs	32	31	30	31	33	32	31.5	3.3
9	24 hrs	35	33	33	34	35	33	33.8	2.9

Fig 12

DISSOLUTION IN 0.1N HCl INNOVATOR

S.No	time	% drug dissolved
S.No	time	sample- 1	sample- 2	sample- 3	sample- 4	sample- 5	sample- 6	MEAN	%RSD
1	0	0	0	0	0	0	0	0	0
2	2 hrs	2	0	0	0	0	0	0.3	25
3	4 hrs	9	4	0	2	0	0	2.5	6.88
4	6 hrs	8	11	2	10	7	4	7	3
5	8 hrs	5	14	4	16	11	6	9.3	3.48
6	10 hrs	3	16	6	20	14	6	10.83	3.85
7	12 hrs	1	18	8	21	11	6	10.83	6.43
8	16 hrs	1	17	10	20	11	7	11	2.94
9	24 hrs	1	24	11	22	10	7	12.5	2.35

F15:

S.No	time	% drug dissolved
S.No	time	sample- 1	sample- 2	sample- 3	sample- 4	sample- 5	sample- 6	MEAN	%RSD
1	0	0	0	0	0	0	0	0	0
2	2 hrs	1	2	1	1	1	3	1.5	55
3	4 hrs	5	8	7	5	5	6	6	21
4	6 hrs	7	11	9	10	11	12	10	17
5	8 hrs	11	12	11	11	9	12	11	9
6	10 hrs	11	14	13	10	11	13	12	12
7	12 hrs	12	13	13	14	14	15	13.5	7
8	16 hrs	15	16	14	15	15	15	15	4
9	24 hrs	18	20	17	18	17	18	18	6

Figure 13:

DISCUSSION:

Based on solubility the dissolution media was selected and it is also official media 0.2% LDAO. Bulk density was found to be 0.37g/ml and CI was 41.11 indicating that drug has to be granulated for the good flow properties.

Melting point was found to be 169.9 ⁰C indicating that drug has less sensitivity for drying temperatures.

Drug – excipient compatibility indicates that the all used excipients in the formulation are compatible with the drug based on RS by HPLC was less than 0.5%.All formulations passed the physical and chemical evaluations.

CONCLUSION:

Formulation-F15 containing Isradipine 10 mg per tablet and developed employing Lactose Monohydrate and Hydroxy ethyl Cellulose in dry mix is similar and equal to the innovator product in respect of all tablets properties and dissolution profile.

No significant change was observed in the drug content, physical properties and dissolution rate of these tablets after the storage period of 2 months at 40^o c and 75%RH. Hence the study resulted in the development of Isradipine Matrix Release Extended tablets comparable to the innovator product for Isradipine fulfilling the objective of the study.

The identified formula shall be utilized for the formulation development and other studies for successful launching of the product as it was proved to be stable and robust, cost effective compared to osmotic device .

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Received on 30.07.2016 Modified on 28.07.2016

Res. J. Pharm. Dosage Form. & Tech. 2016; 8(4): 277-291.

DOI: 10.5958/0975-4377.2016.00039.2