Formulation and Evaluation of Solid Lipid Nanoparticles of Ramipril

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to overcome these problems involves the development

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colloidal carrier systems solid lipid nanoparticles have many advantages and limited disadvantages as compared

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of a wide variety of poorly water soluble drugs due to their biodegradable and biocompatible properties and

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Ramipril, a potent antihypertensive agent has been used

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due to poor absorption, rapid metabolism and elimination,

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Formulation and Evaluation of Solid /ipid Nanoparticles

of Ramipril

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ambaram P

Abdul

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asan Sathali A

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Address for correspondence:3URI$$EGXO+DVDQ6DWKDOL(PDLODEGXOKDVDQ#KRWPDLOFRP

ABSTRACT

6ROLG OLSLG QDQRSDUWLFOHV DUH W\SLFDOO\ VSKHULFDO ZLWK DQ DYHUDJH GLDPHWHU EHWZHHQ DQG QP ,W LV DQ alternative carrier system to tradition colloidal carriers, such as, emulsions, liposomes, and polymeric micro and QDQRSDUWLFOHV5DPLSULOLVDQDQWLK\SHUWHQVLYHDJHQWXVHGLQWKHWUHDWPHQWRIK\SHUWHQVLRQ,WVRUDOELRDYDLODELOLW\ LVDQGLWLVUDSLGO\H[FUHWHGWKURXJKWKHUHQDOURXWH7KLVGUXJKDVPDQ\VLGHHIIHFWVVXFKDVSRVWXUDO hypotension, hyperkalemia, and angioedema, when given as an immediate dosage form. To overcome the side effects and to increase the bioavailability of ramipril, solid lipid nanoparticles of ramipril are prepared by using lipids (glyceryl monostearate and glyceryl monooleate) with stabilizers (tween 80, poloxamer 188, and VSDQ 7KH SUHSDUHG IRUPXODWLRQV KDYH EHHQ HYDOXDWHG IRU HQWUDSPHQW HI¿FLHQF\ GUXJ FRQWHQWin-vitro

drug release, particle size analysis, scanning electron spectroscopy, Fourier transform-infrared studies, and VWDELOLW\$IRUPXODWLRQFRQWDLQLQJJO\FHU\OPRQRROHDWHVWDELOL]HGZLWKVSDQDVVXUIDFWDQWVKRZHGSURORQJHG drug release, smaller particle size, and narrow particle size distribution, as compared to other formulations with different surfactants and lipids.

Key words:&ROORLGDOFDUULHUVUDPLSULOOLSLGPDWUL[VXUIDFWDQWVHQWUDSPHQWHI¿FLHQF\

Access this article online

4uicN Response Code:

Website: www.jyoungpharm.in

DOI:

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of the above fact, the aim of this study is to prepare and characterize the ramipril loaded solid lipid nanoparticles, using glyceryl monostearate and glyceryl monooleate as the lipid matrices and tween 80, poloxamer 188, and span 20, as stabilizers, with a view to improve the dissolution rate

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Given that solid lipid nanoparticles, as an alternative colloidal carrier (transport) system, have the ability to

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MATERIA/S AND MET+ODS

Materials

Ramipril and Poloxamer 188 were obtained as a gift VDPSOH IURP 0DGUDV 3KDUPDFHXWLFDOV &KHQQDL *O\FHU\O PRQRVWHDUDWH >*06@ &'+ 3YW /WG 0XPEDL *O\FHU \O PRQRROHDWH >*02@ 2WWR &KHPLFDOV 0XPEDL 3RO\VRUEDWH 6LVFR 5HVHDUFK /DERUDWRULHV &KHQQDL 6RUELWDQ PRQRODXUDWH /RED &KHPLH0XPEDL&KORURIRUPDQG0HWKDQRO5DQNHP &KHQQDL 'LDO\VLV 0HPEUDQH ² /$ +LPHGLD 0XPEDLZHUHSXUFKDVHGIURPWKHORFDOPDUNHW$OOWKH UHDJHQWVXVHGZHUHRI DQDO\WLFDOJUDGH

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5DPLSULOORDGHG6/1ZHUHSUHSDUHGE\KRWKRPRJHQL]DWLRQ IROORZHGE\WKHXOWUDVRQLFDWLRQPHWKRG[4] _{Ramipril and}

monoglyceride were dissolved in a mixture of methanol

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dissolving the stabilizers (tween 80 or poloxamer 188 or

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The hot aqueous phase was added to the oil phase and

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oil in water emulsion so obtained was sonicated using

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Entrapment efÀciency

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(containing an equivalent to 5 mg of drug) was centrifuged at 20000 rpm for one hour in a refrigerated centrifuge

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suitable dilution with a fresh phosphate buffer saline

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spectrophotometer[12]_{WRFDOFXODWHWKHHQWUDSPHQWHIÀFLHQF\}

using the following formula:

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In vitro drug release

The in vitroUHOHDVHRIUDPLSULOIURPGLIIHUHQW6/1GLVSHUVLRQV ZDVGHWHUPLQHGXVLQJWKHGLDO\VLVEDJGLIIXVLRQWHFKQLTXH[6] $Q DFFXUDWHO\ ZHLJKHG DPRXQW RI 5DPLSULOORDGHG 6/1 GLVSHUVLRQVFRQWDLQLQJWKHGUXJHTXLYDOHQWWRPJZDV WUDQVIHUUHGWRDGLDO\VLVEDJDQGVHDOHG7KHVHDOHGEDJZDV

then suspended in a beaker containing 250 ml of phosphate

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intervals from the receptor compartment up to 12 hours

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drug content was determined spectrophotometrically by measuring the absorbance at 207 nmusing the respective

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Formulation Solid lipid :9 Surfactant :9 Entrapment HI¿FLHQF\ “6'

F1 GMS 6 Tween 80 1.0 78.72 ± 0.64

F2 GMS 6 Tween 80 1.5 80.06 ± 0.47

F3 GMS 6 Tween 80 2.0 81.22 ± 0.52

F4 GMS 6 Poloxamer 188 1.0 81.97 ± 0.79 F5 GMS 6 Poloxamer 188 1.5 84.13 ± 0.32 F6 GMS 6 Poloxamer 188 2.0 85.70 ± 0.26

F7 GMS 6 Span 20 1.0 72.50 ± 0.79

F8 GMS 6 Span 20 1.5 74.85 ± 0.10

F9 GMS 6 Span 20 2.0 76.64 ± 0.11

F10 GMO 6 Tween 80 1.0 75.24 ± 0.05

F11 GMO 6 Tween 80 1.5 76.62 ± 0.53

F12 GMO 6 Tween 80 2.0 77.59 ± 0.18

F13 GMO 6 Poloxamer 188 1.0 79.82 ± 0.24 F14 GMO 6 Poloxamer 188 1.5 84.48 ± 0.45 F15 GMO 6 Poloxamer 188 2.0 86.40 ± 0.24

F16 GMO 6 Span 20 1.0 74.97 ± 0.32

F17 GMO 6 Span 20 1.5 79.34 ± 0.17

F18 GMO 6 Span 20 2.0 82.71 ± 0.4 4

receptor medium as a blank, to calculate the amount of drug

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one drop of sample was taken from each selected formulated nanosuspension and diluted in 10 ml of

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Stability studies

Stability studies were carried out for the formulations having high entrapment efficiency by storing the

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RESU/TS AND DISCUSSION

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Entrapment efficiency is an important parameter for

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optimal encapsulation efficiency, several factors were varied, including the type and concentration of the lipid

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concentration of the surfactant increased the entrapment

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of the drug in the lipid on increasing the concentration

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containing span 20 as surfactants showed lower entrapment

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different nonionic surfactants, and decreased in the order

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In vitro drug release

The in vitroGUXJUHOHDVHSURÀOHRI UDPLSULOIURPYDULRXV 6/1IRUPXODWLRQVLVVKRZQLQ>)LJXUH@7KHin vitro release

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concentration of the surfactant there was an increase in

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These formulations showed a decrease in the drug release on the increase of the concentration of surfactant, which

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release was Poloxamer 188 > Tween 80 > Span 20 on the

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higher drug release than the formulations containing

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leading to lower drug expulsion from the imperfect lattice,

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a lower melting point could produce a controlled release

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Glyceryl monostearate > Glyceryl monooleate on the basis

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amount of drug released was much slower and controlled

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lipid matrix, with Span 20 as the surfactant, than that from

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Particle size analysis

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concentration on the particle size distribution of

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Ramipril-loaded solid lipid nanoparticles, prepared by

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phenomenon could be attributed to the melting point

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from the hot homogenized condition resulting in an

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could be explained due to the higher molecular weight of poloxamer 188 and higher HLB value of poloxamer 188

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increased in the order of Poloxamer 188 > Tween 80 >

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nanoparticles had a spherical shape with a smooth surface

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FT-IR studies

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the spectra it was observed that there was no major shifting, as well as, no loss of functional peaks between the spectra of

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Figure 2: Comparison of in vitroFTWITGNGCUGQH5.0RTGRCTGFD[WUKPI )/5)/1CPFRWTGFTWIUQNWVKQP

100

80

60

40

20

0

0 100 200 300 400 500 600 700 800

Time in minutes

Cumulative % drug release

GMS 6% + Span 20 1.0% GMO 6% + Span 20 2.0% Pure drug solution

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400 350 300 250 200 150 100 50 0

Particle size (nm)

145 290

334

104

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GMO 6% + PF - 68 2.0%

GMS 6% + T - 80 2.0%

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Stability studies

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to more drug expulsion from the lipid matrices at higher

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ultrasound dispersion method was a useful method for the successful incorporation of the poor

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range particles were obtained, the bioavailability might

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nanoparticles provide controlled release of the drug

and these systems are used as drug carriers for lipophilic drugs, to enhance the bioavailability of poorly water-soluble drugs through nanoparticles, as a drug delivery

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REFERENCES

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Source of Support: Nil, ConÀict of Interest: None declared.

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F9 76.64 76.32 73.56 74.47 69.19

F12 77.59 77.02 74.02 75.81 70.01

F15 86.40 86.00 85.26 83.16 81.38

F18 82.71 82.15 81.86 81.57 77.69

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