nuvaring  (Merck & Co)

Journal: Pharmaceutics

Article Title: Next-Generation Contraceptive Intravaginal Ring: Comparison of Etonogestrel and Ethinyl Estradiol In Vitro and In Vivo Release from 3D-Printed Intravaginal Ring and NuvaRing

doi: 10.3390/pharmaceutics16081030

Figure Lengend Snippet: Illustration of IVR manufacturing and loading equations for ENG and EE. ( A ) Schematic of IVR manufacturing with traditional hot-melt extrusion and injection molding. Drugs (ENG and EE) and copolymer (EVA) are poured into the hopper of the injection molding machine. Material is heated and uniformly mixed via hot-melt extrusion and injected into the final IVR mold. Once cooled, the machine ejects the final ENG/EE EVA IVR (NuvaRing). Figure made with BioRender.com. ( B ) IVR manufacturing with CLIP 3D printing (CLIP IVR). Projection of UV light onto photoactive resin (SIL30) promotes polymerization and solidification of the UV-cured IVR. Incorporation of oxygen via an oxygen-permeable window generates a region of uncured resin, known as the ‘dead zone’, to prevent part-attachment to the window. After the UV cure, the IVR undergoes a thermal cure to complete the fabrication process to produce the final product. ENG/EE was incorporated into the IVR via absorption as the IVR swells upon immersion in a drug-containing solution, promoting drug uptake. ( C ) Image of CLIP IVR ( left ) and NuvaRing ( right ). ( D ) Mass and dimensions of CLIP IVR ( n = 3) and NuvaRing ( n = 1). ( E , F ) Loading equations of ENG and EE in CLIP IVR, respectively, as previously developed and validated .

Article Snippet: Drug-loaded CLIP LOW IVRs ( n = 4) and NuvaRing ( n = 1) were placed in a glass chamber at 40 °C/75% relative humidity (RH) in a Fisher Scientific Isotemp Incubator (Pittsburgh, PA, USA) [ ] for 90 days with previously described methods [ ].

Techniques: Injection

Journal: Pharmaceutics

Article Title: Next-Generation Contraceptive Intravaginal Ring: Comparison of Etonogestrel and Ethinyl Estradiol In Vitro and In Vivo Release from 3D-Printed Intravaginal Ring and NuvaRing

doi: 10.3390/pharmaceutics16081030

Figure Lengend Snippet: In vitro release of ENG/EE from CLIP LOW IVR and NuvaRing. ( A ) Cumulative μg in vitro release of ENG/EE from CLIP LOW IVR and NuvaRing. ( B ) Cumulative μg in vitro release of ENG/EE from CLIP LOW IVR and NuvaRing after 90 days of storage under accelerated stability conditions (40 °C/75% relative humidity). ( C , D ) Summary of release kinetics of in vitro release of ENG/EE from CLIP LOW IVR and NuvaRing at baseline and after 90 days of storage under accelerated stability conditions, respectively. BLOD represents ‘below limit of detection’ from HPLC analysis. CLIP LOW IVR release studies were performed in triplicate ( n = 3) and NuvaRing in vitro release studies were performed with n = 1. All release studies were performed in SVF + 2% Solutol at pH 4 release media at 37 °C. The maximum standard deviation for in vitro cumulative release was less than 2%.

Article Snippet: Drug-loaded CLIP LOW IVRs ( n = 4) and NuvaRing ( n = 1) were placed in a glass chamber at 40 °C/75% relative humidity (RH) in a Fisher Scientific Isotemp Incubator (Pittsburgh, PA, USA) [ ] for 90 days with previously described methods [ ].

Techniques: In Vitro, Standard Deviation

Journal: Pharmaceutics

Article Title: Next-Generation Contraceptive Intravaginal Ring: Comparison of Etonogestrel and Ethinyl Estradiol In Vitro and In Vivo Release from 3D-Printed Intravaginal Ring and NuvaRing

doi: 10.3390/pharmaceutics16081030

Figure Lengend Snippet: Pharmacokinetics of CLIP LOW IVR and NuvaRing in sheep. ENG/EE levels in sheep (average ± standard deviation) from CLIP LOW IVR ( n = 4) and NuvaRing ( n = 4) in ( A ) plasma, ( B ) vaginal tissue and ( C ) vaginal fluids. LLOQ of ENG in plasma, vaginal tissue and vaginal fluid is 0.2 ng/mL, 17 ng/g and 0.215 ng/swab, respectively. LLOQ of EE in plasma, vaginal tissue and vaginal fluid is 0.005 ng/mL, 4.2 ng/g and 0.108 ng/swab, respectively. Samples that were below the limit of quantification were represented as LLOQ/2. ( D , E ) Summary table of residual drug quantification and estimated in vivo release rates after CLIP LOW IVR and NuvaRing removal, respectively. Individual replicates are shown in .

Article Snippet: Drug-loaded CLIP LOW IVRs ( n = 4) and NuvaRing ( n = 1) were placed in a glass chamber at 40 °C/75% relative humidity (RH) in a Fisher Scientific Isotemp Incubator (Pittsburgh, PA, USA) [ ] for 90 days with previously described methods [ ].

Techniques: Drug discovery, Standard Deviation, Clinical Proteomics, In Vivo

Journal: Pharmaceutics

Article Title: Next-Generation Contraceptive Intravaginal Ring: Comparison of Etonogestrel and Ethinyl Estradiol In Vitro and In Vivo Release from 3D-Printed Intravaginal Ring and NuvaRing

doi: 10.3390/pharmaceutics16081030

Figure Lengend Snippet: Sheep pharmacokinetics of ENG/EE after 92 days of CLIP HIGH IVR administration. ( A ) Study design of a 92-day PK study with CLIP HIGH IVR in female sheep. ENG/EE concentrations in sheep ( n = 3 sheep that underwent the entire 92-day study) in ( B ) plasma, ( C ) vaginal tissue and ( D ) vaginal fluids from CLIP LOW IVR, CLIP HIGH IVR and NuvaRing. Each curve represents the average ± standard deviation. Dashed lines indicated the last concentration (day 21) of ENG (dashed green line) and (dashed blue line) from the NuvaRing sheep study extended to 92 days for comparative purposes only. Individual replicates for sheep that underwent the 92-day study duration with CLIP HIGH IVR are shown in . Individual replicates for CLIP LOW IVR and NuvaRing are shown in .

Article Snippet: Drug-loaded CLIP LOW IVRs ( n = 4) and NuvaRing ( n = 1) were placed in a glass chamber at 40 °C/75% relative humidity (RH) in a Fisher Scientific Isotemp Incubator (Pittsburgh, PA, USA) [ ] for 90 days with previously described methods [ ].

Techniques: Drug discovery, Clinical Proteomics, Standard Deviation, Concentration Assay

Journal: Pharmaceutics

Article Title: Next-Generation Contraceptive Intravaginal Ring: Comparison of Etonogestrel and Ethinyl Estradiol In Vitro and In Vivo Release from 3D-Printed Intravaginal Ring and NuvaRing

doi: 10.3390/pharmaceutics16081030

Figure Lengend Snippet: Sheep safety analysis for NuvaRing. Histological images of vaginal biopsies from sheep administered NuvaRing (with higher magnification insert) at ( A ) day 0, ( B ) day 1, ( C ) day 3, ( D ) day 7, ( E ) day 14 and ( F ) day 21 post-IVR insertion. Red arrowheads denote examples of eosinophils. Black arrows denote parakeratosis. Scale bar = 50 µm. ( G ) Histological scoring summary based on H&E images. Individual scores from each sheep are presented in . Day 0 represents the baseline with no IVR use.

Article Snippet: Drug-loaded CLIP LOW IVRs ( n = 4) and NuvaRing ( n = 1) were placed in a glass chamber at 40 °C/75% relative humidity (RH) in a Fisher Scientific Isotemp Incubator (Pittsburgh, PA, USA) [ ] for 90 days with previously described methods [ ].

Techniques: