Bhalerao et al Journal of Drug Delivery & Therapeutics. 2019; 9(3):212-221
ISSN: 2250-1177 [212] CODEN (USA): JDDTAO
Available online on 15.05.2019 at http://jddtonline.info
Journal of Drug Delivery and Therapeutics
Open Access to Pharmaceutical and Medical Research
© 2011-18, publisher and licensee JDDT, This is an Open Access article which permits unrestricted
non-commercial use, provided the original work is properly cited
Open Access Research Article
Formulation of Solid Lipid Nanoparticles of Cilnidipine for the Treatment of
Hypertension
Bhalerao Aparna
1
*, Choudhari Pankaj
2
1
JSPM’s Charak College of Pharmacy and Research, Wagholi, Pune, Maharashtra-412207
2
Micro Labs Limited, Chandivali, Andheri East, Mumbai, Maharashtra-400072
ABSTRACT
Cilinidipine is a fourth generation N and L-type calcium channel antagonists used alone or in combination with another drug to treat
hypertension. Cilnidipine is poorly water -soluble, BCS class II drug with 6 to 30 percent oral bioavailability due to first pass metabolism. So to
protect the drug from degradation and improve its dissolution, solid lipid nanoparticles were prepared. Glyceryl monostearate was selected as
lipid while span 20: tween 20 were selected as surfactant blends. The formulations were evaluated for various parameters, as percent
transmittance, drug content, percent encapsulation efficiency; percent drug loading, In vitro drug release and particle size. Optimized
formulation was lyophilized using lactose as a cryo-protectant. The lyophilized formulation was evaluated for micromeritic properties, particle
size and in vitro dissolution. It was further evaluated for DSC, XRD, and SEM. Percent encapsulation efficiency and percent drug loading of
optimized formulation (F3) were 78.66percent and 9.44percent respectively. The particle size of F3 formulation without drug was 204 nm and
with the drug was 214 nm. The particle size of the reconstituted SLN was 219 nm. In DSC study, no obvious peaks for cilnidipine were found in
the SLN of cilnidipine indicated that the cilnidipine must be present in a molecularly dissolved state in SLN. In X-ray diffractometry absence of
peaks representing crystals of cilnidipine in SLN indicated that the drug was in an amorphous or disordered crystalline phase in the lipid
matrix. Thus, solid lipid nanoparticle formulation is a promising way to enhance the dissolution rate of cilnidipine.
Keywords: Cilnidipine, Solid Lipid Nanoparticle, Hypertension
Article Info: Received 24 March 2019; Review Completed 03 May 2019; Accepted 06 May 2019; Available online 15 May 2019
Cite this article as:
Bhalerao A, Choudhari P, Formulation of Solid Lipid Nanoparticles of Cilnidipine for the Treatment of Hypertension,
Journal of Drug Delivery and Therapeutics. 2019; 9(3):212-221 http://dx.doi.org/10.22270/jddt.v9i3.2849
*Address for Correspondence:
Dr Aparna V. Bhalerao, Associate Professor, JSPM's Charak College of Pharmacy and Research, Wagholi, Pune,
Maharashtra, India-412207
INTRODUCTION
Hypertension also called a silent killer is one of the most
important risk factors for cardiovascular disease, a leading
cause of death
1
. Various classes of a drug as diuretics, α-
blockers, b-blockers, angiotensin-converting enzyme (ACE)
inhibitors, angiotensin II type 1 receptor blockers (ARB),
and organic calcium channel blockers (CCBs) are used alone
or in combination for the treatment of hypertension. Short-
acting calcium channel antagonists decrease the blood
pressure by vasodilation but are unable to decrease the
blood pressure associated with sympathetic overactivity
which is a secondary to the vasodilation
1,2
. To lessen or
avoid the neurohormonal activation caused by short-acting
calcium channel blockers (CCB), fourth generation
dihydropyridine (DHP) based N and L-type calcium channel
antagonists like cilnidipine have been developed that have
potential clinical benefits: gradual onset of action and a long
duration of effects along with renal protection by decreasing
the activity of the sympathetic nervous system (SNS) and the
renin-angiotensin system
2,3,4
. Cilnidipine is highly lipophilic,
BCS class II drug with very low water solubility, which limits
the dissolution rate of cilnidipine in water and in turn oral
bioavailability. All calcium channel blocker undergoes
extensive hepatic first-pass metabolism
5
, and are also
substrates for p-glycoprotein resulting in limited oral
bioavailability. Solid lipid nanoparticles(SLN) dissolve the
lipophilic drug in lipid which protects the drug from
enzymatic degradation and facilitates the transport of drug
through lymphatic route thus avoids the hepatic first pass
metabolism
6,7,8
.
MATERIAL AND METHODS
Cilnidipine was obtained as gift sample from JB Chemical,
Mumbai, India Labrafil 1944, Compritol, Precirol were
obtained as gift samples from Gattefosse Corporation,
France, poloxamer 407 was obtained from BASF India, oleic
acid, Tween 20, Tween 80, propylene glycol, polyethylene
glycol, Span 60, isopropyl myristate, ethyl oleate, isopropyl
palmitate, and glyceryl monostearate, were purchased from
Research Lab Ltd. All other chemicals used were of analytical
grade.