Preformulation and characterization of raloxifene-loaded lipid nanoparticles for transdermal administration

被引:10
作者
Alves, Guilherme L. [1 ]
Teixeira, Fernanda V. [1 ]
da Rocha, Priscila Bianca Rodrigues [1 ]
Krawczyk-Santos, Anna Paula [1 ]
Andrade, Ligia Marquez [1 ]
Cunha-Filho, Marcilio [2 ]
Marreto, Ricardo N. [1 ]
Taveira, Stephania F. [1 ]
机构
[1] Univ Fed Goias UFG, Lab Nanosyst & Drug Delivery Devices NanoSYS, Sch Pharm, Setor Leste Universitario, Rua 240,Setor Leste Univ, BR-74605170 Goiania, Go, Brazil
[2] Univ Brasilia, Lab Food Drug & Cosmet LTMAC, Sch Hlth Sci, Brasilia, DF, Brazil
关键词
Raloxifene; Drug-excipient compatibility; Thermal analysis; Isothermal stress testing; Skin permeation; Transdermal delivery; CARRIERS NLC; DRUG; DELIVERY; COMPATIBILITY; EXCIPIENTS; FORMULATIONS; RELEASE; DESIGN; ENCAPSULATION; OPTIMIZATION;
D O I
10.1007/s13346-021-00949-y
中图分类号
TH7 [仪器、仪表];
学科分类号
0804 ; 080401 ; 081102 ;
摘要
Transdermal administration of raloxifene hydrochloride (RLX)-loaded nanostructured lipid carriers (NLCs) has been proposed to circumvent its low oral bioavailability (2%). Preformulation studies were carried out to evaluate drug-excipient compatibility of various adjuvants commonly used for NLC preparation (waxes, cholesterol, compritol, gelucire, span 60, span 80, span 85, tween 80, poloxamer 188, oleic acid, caprylic/capric triglyceride, and castor oil). It was used differential scanning calorimetry (DSC), isothermal stress testing (IST), and solubility studies. The most promising excipients were chosen for NLC obtention, and full characterization was done, including in vitro skin permeation. DSC curves suggested drug-excipient interaction among some compounds, and the IST study showed incompatibility of RLX with waxes, compritol, cholesterol, span 60, and poloxamer 188. Solubility studies helped select gelucire, caprylic/capric triglyceride, span 80, and tween 80 for NLC production. Twelve NLCs were obtained (NLC1 to NLC12), but NLC7 and NLC8 were the most promising ones. In vitro release studies demonstrated that NLC7 and NLC8 were able to control RLX release (14.74 and 9.07% at 24 h, respectively) compared with the unloaded drug (> 90% at 24 h). Unloaded RLX did not permeate the diffusion cells' receptor medium and showed higher drug skin retention (11-fold) than RLX-loaded NLC. NLC reduced RLX skin retention, favoring drug permeation to deeper skin layers. NLC7 increased drug flux is 2.4-fold. NLC7 is a promising formulation for RLX transdermal drug delivery.
引用
收藏
页码:526 / 537
页数:12
相关论文
共 52 条
[1]   Skin delivery of antioxidant surfactants based on gallic acid and hydroxytyrosol [J].
Alonso, Cristina ;
Lucas, Ricardo ;
Barba, Clara ;
Marti, Meritxell ;
Rubio, Laia ;
Comelles, Francesc ;
Carlos Morales, Juan ;
Coderch, Luisa ;
Luis Parra, Jose .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 2015, 67 (07) :900-908
[2]   Improved tacrolimus skin permeation by co-encapsulation with clobetasol in lipid nanoparticles: Study of drug effects in lipid matrix by electron paramagnetic resonance [J].
Andrade, Ligia Marquez ;
Dantas Silva, Luis Antonio ;
Krawczyk-Santos, Anna Paula ;
Amorim, Isabella Cristina de S. M. ;
Rodrigues da Rocha, Priscila Bianca ;
Lima, Eliana Martins ;
Anjos, Jorge Luiz V. ;
Alonso, Antonio ;
Marreto, Ricardo Neves ;
Taveira, Stephania Fleury .
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 2017, 119 :142-149
[3]   Overcoming the stratum corneum barrier: a nano approach [J].
Banerjee, Rinti .
DRUG DELIVERY AND TRANSLATIONAL RESEARCH, 2013, 3 (03) :205-208
[4]   Enhanced intestinal absorption and bioavailability of raloxifene hydrochloride via lyophilized solid lipid nanoparticles [J].
Burra, Madhu ;
Jukanti, Raju ;
Janga, Karthik Yadav ;
Sunkavalli, Sharath ;
Velpula, Ashok ;
Ampati, Srinivas ;
Jayaveera, K. N. .
ADVANCED POWDER TECHNOLOGY, 2013, 24 (01) :393-402
[5]   Drug-excipient compatibility screening-Role of thermoanalytical and spectroscopic techniques [J].
Chadha, Renu ;
Bhandari, Swati .
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 2014, 87 :82-97
[6]   Selection of excipients for the development of carvedilol loaded lipid-based drug delivery systems [J].
Dantas Silva, Luis Antonio ;
Cintra, Emilio Ramos ;
Pineze Alonso, Ellen Cristine ;
Alves, Guilherme Liberato ;
Lima, Eliana Martins ;
Taveira, Stephania Fleury ;
Soares da Cunha-Filho, Marcilio Sergio ;
Marreto, Ricardo Neves .
JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY, 2017, 130 (03) :1593-1604
[7]   Evaluation of carvedilol compatibility with lipid excipients for the development of lipid-based drug delivery systems [J].
Dantas Silva, Luis Antonio ;
Teixeira, Fernanda Vieira ;
Serpa, Raphael Caixeta ;
Esteves, Najla Locatelli ;
dos Santos, Rayane Ramos ;
Lima, Eliana Martins ;
Soares da Cunha-Filho, Marcilio Sergio ;
de Souza Araujo, Adriano Antunes ;
Taveira, Stephania Fleury ;
Marreto, Ricardo Neves .
JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY, 2016, 123 (03) :2337-2344
[8]  
Dash S, 2010, ACTA POL PHARM, V67, P217
[9]   Nanoemulsion liquid preconcentrates for raloxifene hydrochloride: optimization and in vivo appraisal [J].
Elsheikh, Manal A. ;
Elnaggar, Yosra S. R. ;
Gohar, Eman Y. ;
Abdallah, Ossama Y. .
INTERNATIONAL JOURNAL OF NANOMEDICINE, 2012, 7 :3787-3802
[10]   Development of Lipid-Shell and Polymer Core Nanoparticles with Water-Soluble Salidroside for Anti-Cancer Therapy [J].
Fang, Dai-Long ;
Chen, Yan ;
Xu, Bei ;
Ren, Ke ;
He, Zhi-Yao ;
He, Li-Li ;
Lei, Yi ;
Fan, Chun-Mei ;
Song, Xiang-Rong .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2014, 15 (03) :3373-3388