Misoprostol is a prostaglandin E1 analogue used to prevent and treat gastric ulcers. It has been commonly used in gynecology and obstetrics, especially for the management of postpartum hemorrhage (PPH). For this purpo...Misoprostol is a prostaglandin E1 analogue used to prevent and treat gastric ulcers. It has been commonly used in gynecology and obstetrics, especially for the management of postpartum hemorrhage (PPH). For this purpose, 1000 μg intrarectal (insertion of five 200 μg tablets) has been recommended as the third line after injectable oxytocin and methylergometrine. We proposed to manufacture a 1000 μg misoprostol suppository by determining formulation, release and stability. The administration facility was also evaluated. Several formulations of misoprostol suppositories were set up and evaluated. Misoprostol tablets and lipophilic bases (Hard fat—Adeps solidus Ph. Eur., Witepsol? H15 and Suppocire? AM and AS2X) were used to obtain suppositories. Surfactants were also tested (polysorbates Tween? 20, Tween? 80 and sodium lauryl sulfate (SLS)). The formula was monitored by the misoprostol release curve with an in vitro test and dosed by a HPLC method. Stability was determined by evaluating the percentage of misoprostol content remaining over the time in suppositories stored at 4℃ and 25℃. Facility of use versus tablets was evaluated by obstetricians of a Swiss regional hospital using a questionnaire. Misoprostol release was facilitated by adding surfactant to the lipophilic base. After 30 minutes, 59% ± 1.4% and 57% ± 8.2% of misoprostol was released with Adeps solidus + 1% SLS and Adeps solidus + 5% Tween 20 respectively. SLS was discarded to the final formula because of its irritating effect. After 7 months, suppositories still contained 94% ± 3.7% misoprostol with storage at 4℃. The administration was considered easier and faster compared with intra rectal use of tablets. The formula, consisting of 5 crushed misoprostol tablets dispersed in a suppository base made of Adeps solidus + 5% Tween? 20, is stable for at least 7 months at 4?C and facilitates the rectal administration of misoprostol in the treatment of PPH.展开更多
Biologicals have been used for decades in biopharmaceutical topical preparations. Because cellular therapies are routinely used in the clinic they have gained significant attention. Different derivatives are possible ...Biologicals have been used for decades in biopharmaceutical topical preparations. Because cellular therapies are routinely used in the clinic they have gained significant attention. Different derivatives are possible from different cell and tissue sources, making the selection of cell types and establishment of consistent cell banks crucial steps in the initial whole-cell bioprocessing. Various cell and tissue types have been used in treatment of skin wounds including autologous and allogenic skin cells, platelets, placenta and amniotic extracts from either human or animal sources. Experience with progenitor cells show that they may provide an interesting cell choice due to facility of out-scaling and known properties for wound healing without scar. Using defined animal cell lines to develop cell-free derivatives may provide initial starting material for pharmaceutical formulations that help in overall stability. Cell lines derived from ovine tissue (skin, muscle, connective tissue) can be developed in short periods of time and consistency of these cell lines was monitored by cellular life-span, protein concentrations, stability and activity. Each cell line had long culture periods up to 37 - 41 passages and protein measures for each cell line at passages 2 - 15 had only 1.4-fold maximal difference. Growth stimulation activity towards two target skin cell lines (GM01717 and CRL-1221;40 year old human males) at concentrations ranging up to 6mg/ml showed 2-3-fold (single extracts) and 3-7-fold (co-cultured extracts) increase. Proteins from co-culture remained stable up to 1 year in pharmaceutical preparations shown by separation on SDS-PAGE gels. Pharmaceutical cell-free preparations were used for veterinary and human wounds and burns. Cell lines and cell-free extracts can show remarkable consistency and stability for preparation of biopharmaceutical creams, moreover when cells are co-cultured, and have positive effects for tissue repair.展开更多
文摘Misoprostol is a prostaglandin E1 analogue used to prevent and treat gastric ulcers. It has been commonly used in gynecology and obstetrics, especially for the management of postpartum hemorrhage (PPH). For this purpose, 1000 μg intrarectal (insertion of five 200 μg tablets) has been recommended as the third line after injectable oxytocin and methylergometrine. We proposed to manufacture a 1000 μg misoprostol suppository by determining formulation, release and stability. The administration facility was also evaluated. Several formulations of misoprostol suppositories were set up and evaluated. Misoprostol tablets and lipophilic bases (Hard fat—Adeps solidus Ph. Eur., Witepsol? H15 and Suppocire? AM and AS2X) were used to obtain suppositories. Surfactants were also tested (polysorbates Tween? 20, Tween? 80 and sodium lauryl sulfate (SLS)). The formula was monitored by the misoprostol release curve with an in vitro test and dosed by a HPLC method. Stability was determined by evaluating the percentage of misoprostol content remaining over the time in suppositories stored at 4℃ and 25℃. Facility of use versus tablets was evaluated by obstetricians of a Swiss regional hospital using a questionnaire. Misoprostol release was facilitated by adding surfactant to the lipophilic base. After 30 minutes, 59% ± 1.4% and 57% ± 8.2% of misoprostol was released with Adeps solidus + 1% SLS and Adeps solidus + 5% Tween 20 respectively. SLS was discarded to the final formula because of its irritating effect. After 7 months, suppositories still contained 94% ± 3.7% misoprostol with storage at 4℃. The administration was considered easier and faster compared with intra rectal use of tablets. The formula, consisting of 5 crushed misoprostol tablets dispersed in a suppository base made of Adeps solidus + 5% Tween? 20, is stable for at least 7 months at 4?C and facilitates the rectal administration of misoprostol in the treatment of PPH.
文摘Biologicals have been used for decades in biopharmaceutical topical preparations. Because cellular therapies are routinely used in the clinic they have gained significant attention. Different derivatives are possible from different cell and tissue sources, making the selection of cell types and establishment of consistent cell banks crucial steps in the initial whole-cell bioprocessing. Various cell and tissue types have been used in treatment of skin wounds including autologous and allogenic skin cells, platelets, placenta and amniotic extracts from either human or animal sources. Experience with progenitor cells show that they may provide an interesting cell choice due to facility of out-scaling and known properties for wound healing without scar. Using defined animal cell lines to develop cell-free derivatives may provide initial starting material for pharmaceutical formulations that help in overall stability. Cell lines derived from ovine tissue (skin, muscle, connective tissue) can be developed in short periods of time and consistency of these cell lines was monitored by cellular life-span, protein concentrations, stability and activity. Each cell line had long culture periods up to 37 - 41 passages and protein measures for each cell line at passages 2 - 15 had only 1.4-fold maximal difference. Growth stimulation activity towards two target skin cell lines (GM01717 and CRL-1221;40 year old human males) at concentrations ranging up to 6mg/ml showed 2-3-fold (single extracts) and 3-7-fold (co-cultured extracts) increase. Proteins from co-culture remained stable up to 1 year in pharmaceutical preparations shown by separation on SDS-PAGE gels. Pharmaceutical cell-free preparations were used for veterinary and human wounds and burns. Cell lines and cell-free extracts can show remarkable consistency and stability for preparation of biopharmaceutical creams, moreover when cells are co-cultured, and have positive effects for tissue repair.
