Encapsulated chlorhexidine for sustained release/antibacterial effects

Transcription

1 Encapsulated chlorhexidine for sustained release/antibacterial effects Fabrice Pirot a, Yves Ducini b, Gérard Trouvé b a: Laboratoire de pharmacie galénique industrielle Faculté de Pharmacie de Lyon b: Seppic, Castres XIX International Conference on Bioencapsulation Amboise, France ; October 58,

2 Encapsulated chlorhexidine for sustained release Seppic subsidiary of air Liquide Group 250 M turnover 650 employees all over the world is producing excipients and active ingredients for pharmaceutical, cosmetics and food industries. is a research driven company with a large expertise in chemical synthesis (surfactants and polymers) and formulation of ready to use compositions July 01 2

3 Encapsulated chlorhexidine for sustained release Excipients Active ingredients Pharmacy Coating compositions SEPIFILM TM Surfactants MONTANOX TM SIMULSOL TM Adjuvants for vaccines MONTANIDE TM Mineral salts GIVOBIO TM Food Cosmetics Coating compositions SEPIFILM TM Non Ionic Surfactants MONTANE TM MONTANOX TM Surfactants APG MONTANOV TM Polymers (thickeners) SEPIGEL TM SIMULGEL TM Antioxydants: EXTRAMEL TM, AROLIA Sweeteners: STEVIA Moisturizing agents: AQUAXYL TM Anti wrinkels: Anti aging agents: TIMECODE TM SEPILIFT DPHP TM Whitening agents: SEPIWHITE TM SURVICODE TM July 01 3

4 Encapsulated chlorhexidine for sustained release And now a new technical platform dedicated to Encapsulation and Delivery Systems Managing several standard complementary technologies: Coating and granulation Coacervation Spray drying Prilling Absorption into porous supports Ion exchange resins Collaborating with universities and other partners to develop and promote original technologies. Developing microcapsules at the lab and pilot scale and manufacturing at the industrial level July 01 4

5 Background (I) Biocides as Antiseptic Medical hygiene and healthcare: cutaneous, ocular, dental and nasal routes Biocides as Preservatives Pharmaceutical products Cosmetics Food industry 5

6 Background (II) Nosocomial infections and morbidity and mortality Transmission of nosocomial pathogen by hands Need of effective antiseptic procedures Incorporation of antiseptics into handwashing agents Frequent use of antiseptics : contact dermatitis and allergies 6

7 Biocide encapsulation for sustained antibacterials effects: Nanochlorex concept poly caprolactone chlorhexidine base lipophilic core Hydrophilic polymer /surfactant dicationic chlorhexidine 7

8 Bactericidal activities of chlorhexidine (CHX) loaded nanocapsules vs. chlorhexidine digluconate against Staplylococcus epidermidis Comparison of sustained antibacterial effect of : ( ) Nanochlorex 0.6% CHX ( ) unloaded Nanochlorex ( ) CHX digluconate 1% applied to human skin for 3 min, then contaminated successively by Staphylococcus epidermidis at time 3 min, 4 h, 8 h 8 8

9 Comparison of sustained antibacterial effect of : ( ) Nanochlorex ( ) Purell : 62% (v/v) ethanolbased gel applied to human skin for 5 min, then contaminated successively by Staphylococcus epidermidis at time 5 min, 1 h, 2 h, and 3 h. 9 9

10 Immediate and sustained antibacterial effect of Nanochlorex : confirmed against resident and transient hand flora in humans chlorhexidine carrier system: improvement of drug targeting to bacteria and reduction of further bacterial growth onto the skin. Nanochlorex : as effective as 2propanol 60% (v/v) and 62% (v/v) ethanolbased hand gel (Purell ) within 30 s of application Nanochlorex : more efficient than 2propanol 60% (v/v) against anaerobic bacteria and longlasting antibacterial activity higher than that of Purell. Nanochlorex : a promising approach for hygienic hand disinfection in care practice where multiple procedures are performed. 10

11 Nanochlorex mechanism cationic metal 11

12 Chlorhexidine loaded nanocapsule: Concentration : 0.6 % Size : ~ 300 nm; : ~ 30 à 40 mv Sodium CMC gel structure 12

13 Solventfree production of polymeric nanocapsules Patent pending in EP and US Priority date: April 18, 2008 (FR ) VOD 13

14 Part. I: Polymeric/oily phase 14

15 Part.II: hydrocolloïd and nanocapsules formation 15

16 Polymer wall as controlled diffusion parameter Oily phase volume 6.00 cm³ Nanocapsule volume (VNC) cm³ Nanocapsule number 424 T Polymer mass a 130 mg Polymer wall thickness (nm) b 2.5 H VL VNC 300 mg 5.0 r1 r2 550 mg 10 a : Nanocapsules number x V PCL/NC V PCL/NC = VNC VL = 4/3 π (r1)³ 4/3 π (r2)³ b: r1 r2 16

17 Polymer wall as controlled diffusion parameter Oily phase volume 0.55 cm³ Nanocapsule volume (VNC) cm³ Nanocapsule number 39 T Polymer mass a 125 mg Polymer wall thickness (nm) b 13 H VL VNC r1 r2 a : Nanocapsules number x V PCL/NC V PCL/NC = VNC VL = 4/3 π (r1)³ 4/3 π (r2)³ b: r1 r2 17

18 Conclusion Encapsulation of biocide sustains antiseptic effects Solventfree production of polymeric nanocapsules : Cost reduction Fast Safe Versatile (FAQ) 18

19 Nanochlorex 19