1.
The disintegration behaviour of capsules in fed subjects: a comparison of hypromellose (carrageenan) capsules and standard gelatin capsules.
Jones, BE, Basit, AW, Tuleu, C
International journal of pharmaceutics. 2012;(1-2):40-3
Abstract
Two-piece hard shell capsules made from hypromellose (or hydroxypropyl methylcellulose, HPMC) containing carrageenan as a gelling agent have been proposed as an alternative to conventional gelatin capsules for oral drug delivery. We have previously compared the disintegration of hypromellose(carrageenan) (Quali-V(®)) and gelatin capsules (Qualicaps) in fasted human subjects using the technique of gamma scintigraphy. This second study used the same technique with both fasted and fed human subjects. Size 0 capsules were filled with powder plugs made from lactose and did not contain croscarmellose as in the original study. The capsules were separately radiolabelled with indium-111 and technetium-99m. Both capsules were administered simultaneously with 180ml water to eight healthy male subjects following an overnight fast. Each volunteer was positioned in front of the gamma camera and sequential 60s images were acquired in a continuous manner for 30min. The mean (±S.D.) disintegration time in the fasted state for the hypromellose(carrageenan) capsules was 8±2min and for gelatin 7±3min. These results were not statistically different from the data in the original study and show that the removal of the croscarmellose had no effect on the results. The mean (±S.D.) disintegration time in the fed state for the hypromellose(carrageenan) capsules was 16±5min and for the gelatin capsules was 12±4min. There was no statistical difference between the hypromellose(carrageenan) and gelatin capsules in either the fed or fasted state.
2.
Hyaluronan-Irinotecan improves progression-free survival in 5-fluorouracil refractory patients with metastatic colorectal cancer: a randomized phase II trial.
Gibbs, P, Clingan, PR, Ganju, V, Strickland, AH, Wong, SS, Tebbutt, NC, Underhill, CR, Fox, RM, Clavant, SP, Leung, J, et al
Cancer chemotherapy and pharmacology. 2011;(1):153-63
Abstract
PURPOSE The objective of this study was to conduct a randomised phase II study in second-line metastatic colorectal cancer with the purpose of confirming preliminary clinical data indicating that the formulation of irinotecan with the drug carrier, hyaluronan (HA) reduced toxicity of the drug. METHODS Irinotecan-naïve patients were randomized to receive either irinotecan (350 mg/m(2)) or HA-Irinotecan (HA 1,000 mg/m(2) and irinotecan at 350 mg/m(2)) every 3 weeks for a maximum of eight cycles. RESULTS Seventy-six patients (41 HA-Irinotecan and 35 irinotecan-alone) were enrolled. There was no significant difference in any individual, or overall, grade 3 or 4 toxicity. There was a trend for increased diarrhea in the HA-Irinotecan-treated patients (20 versus 9%; P = 21), potentially explained by a disproportionate number of baseline toxicity-associated risk factors in this treatment group. The median number of cycles completed was six for HA-Irinotecan patients and two for irinotecan-alone patients (P = 0.005). When compared to the control arm, HA-Irinotecan patients had a significantly longer median progression-free survival of 5.2 versus 2.4 months (P = 0.017) and time to treatment failure (4 vs. 1.8 months; P = 0.007). Median overall survival was 10.1 months for HA-Irinotecan compared to 8.0 months for irinotecan patients (P = 0.196). CONCLUSION Further studies are required to define the safety of the formulation of irinotecan with HA. While this study was not adequately powered to demonstrate survival differences, these phase II data indicated HA-Irinotecan to be a promising therapy demonstrating improved efficacy compared to irinotecan-alone.
3.
Initial fusion rates with recombinant human bone morphogenetic protein-2/compression resistant matrix and a hydroxyapatite and tricalcium phosphate/collagen carrier in posterolateral spinal fusion.
Glassman, SD, Dimar, JR, Carreon, LY, Campbell, MJ, Puno, RM, Johnson, JR
Spine. 2005;(15):1694-8
Abstract
STUDY DESIGN Prospective, randomized, unblinded study of iliac crest bone graft (ICBG) versus recombinant human bone morphogenetic protein-2/compression resistant matrix (rhBMP-2/CRM)in a posterolateral instrumented fusion procedure. OBJECTIVES Document initial radiographic characteristics, based on computed tomography, with rhBMP-2/CRM for posterolateral fusion at 6 and 12-month intervals. SUMMARY OF BACKGROUND DATA As the acceptance of INFUSE bone graft as an ICBG replacement becomes more widespread, surgeons have begun to study applications for rhBMP-2 in posterior spinal fusion. Preclinical studies have examined variables including carrier composition, rhBMP-2 concentration, and rhBMP-2 dose. Pilot studies have been performed with encouraging initial results. METHODS Patients with single level lumbar degenerative disease were enrolled in a randomized study of ICBG versus rhBMP-2/CRM in a posterolateral instrumented fusion procedure. Computed tomography scans at 6 and 12 months were graded as demonstrating no fusion (grade 1), partial or limited unilateral fusion (grade 2), partial or limited bilateral fusion (grade 3), solid unilateral fusion (grade 4), or solid bilateral fusion (grade 5). RESULTS At our institution, 74 patients (38 rhBMP-2/CRM, 36 ICBG) reached minimum 1-year follow-up and were included in this analysis. Mean fusion grade (scale1-5) at 6 months after surgery was 4.35 in the rhBMP-2/CRM group versus 3.09 in the ICBG group (P < 0.0001). At 1 year after surgery mean fusion grade was 4.62 in the rhBMP-2/CRM group versus 3.77 in the ICBG group (P < 0.0023). CONCLUSIONS These early results are encouraging and suggest a more rapid incorporation and development of the fusion mass with rhBMP-2/CRM than iliac crest autograft in a single level posterior instrumented fusion.
4.
Chlorhexidine release from an experimental glass ionomer cement.
Palmer, G, Jones, FH, Billington, RW, Pearson, GJ
Biomaterials. 2004;(23):5423-31
Abstract
Glass ionomer cements (GIC) can potentially be used as matrices for the slow release of active species, as has been shown previously for fluoride ions. This study investigated the use of an experimental GIC as a carrier for the release of chlorhexidine acetate (CHA) at included concentrations ranging from 0.5% to 13.0% of CHA by weight. Release into water was examined using high-performance liquid chromatography. All measurable chlorhexidine was released within 22 h1/2, however this was less than 10% of the total mass incorporated in the specimens. An increased percentage of CHA incorporated into the powder gave an increased release into the surrounding water. The bulk of the CHA was retained within the cement. For comparison, the surface chemistry of a CHA-containing GIC was examined using X-ray photoelectron spectroscopy before and after prolonged immersion in water. This confirmed retention of a large amount of CHA. Spectra after leaching appeared very similar to those from a CHA-free GIC after immersion in a CHA solution. In order to explore the effect of CHA-inclusion on the cement properties, compressive strengths, working and setting times were also measured. In general, compressive strengths were found to be decreased in direct proportion to the quantity of CHA added, while working and setting times increased.