Improved Bioavailability with Dry Powder Cannabidiol…
Aug 16, 2021 15:45:23 GMT -5
nxc2, prcgorman2, and 6 more like this
Post by lazyb767 on Aug 16, 2021 15:45:23 GMT -5
jpharmsci.org/article/S0022-3549(21)00413-5/fulltext
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Administration of CBD as a dry powder via the DreamBoat inhaler resulted in a more rapid and consistent response compared with oral CBD (mean time to Cmax of 4 minutes inhaled versus 2 hours oral). Although the DPI CBD formulation contained a much lower dose than oral CBD, the DPI resulted in a peak CBD concentration nearly 3-fold higher than oral CBD. When adjusted for dose, the maximum CBD concentration was 71-fold greater and overall exposure was 9-fold greater for DPI CBD compared with oral CBD. Drug absorption with DPI CBD was more rapid and robust than oral CBD, consistent with direct delivery to the deep lung, because the DPI formulation avoids the erratic absorption and first-pass hepatic metabolism of oral administration.23
Following hepatic metabolism of oral CBD, many metabolites circulate systemically, with 7-COOH-CBD most abundant.26 In this study, the DPI CBD formulation resulted in a 25-fold reduction in the ratio of the inactive metabolite 7-COOH-CBD to CBD compared with the oral formulation. These data support the finding that inhalation of CBD formulated as a dry powder is a more efficient administration route than oral delivery. Following inhalation, a larger fraction of the active parent CBD circulates in the blood compared with the inactive metabolite. Additionally, these data show that inhalation delivery has the potential to reduce the concerns of hepatotoxicity associated with oral CBD administration. CBD absorbed from the gastrointestinal tract goes directly to the liver, while CBD absorbed through the lung bypasses first-pass hepatic metabolism.
The oral and inhaled dry powder CBD formulations were generally safe and well-tolerated following a single administration. A few patients who received the DPI CBD formulation experienced a dry, throat-clearing cough following inhalation, not considered an AE by the investigator, that was transient and resolved; this was observed in other studies using the FDKP excipient in patients naïve to dry-powder inhalers.16 Although one participant in the DPI CBD group experienced mild laboratory abnormalities, these were considered unrelated to the study treatment because the participant had engaged in strenuous weight lifting immediately prior to the study and the elevations were expected post exercise. Participants in this study reported that neither the oral nor DPI CBD formulations impacted somnolence as measured by the participant-reported Stanford Sleepiness Scale. Two participants who received the DPI formulation did not inhale properly and the powder did not discharge completely from the inhaler; to prevent this issue, additional inhaler instruction and training will be provided in future studies…
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Administration of CBD as a dry powder via the DreamBoat inhaler resulted in a more rapid and consistent response compared with oral CBD (mean time to Cmax of 4 minutes inhaled versus 2 hours oral). Although the DPI CBD formulation contained a much lower dose than oral CBD, the DPI resulted in a peak CBD concentration nearly 3-fold higher than oral CBD. When adjusted for dose, the maximum CBD concentration was 71-fold greater and overall exposure was 9-fold greater for DPI CBD compared with oral CBD. Drug absorption with DPI CBD was more rapid and robust than oral CBD, consistent with direct delivery to the deep lung, because the DPI formulation avoids the erratic absorption and first-pass hepatic metabolism of oral administration.23
Following hepatic metabolism of oral CBD, many metabolites circulate systemically, with 7-COOH-CBD most abundant.26 In this study, the DPI CBD formulation resulted in a 25-fold reduction in the ratio of the inactive metabolite 7-COOH-CBD to CBD compared with the oral formulation. These data support the finding that inhalation of CBD formulated as a dry powder is a more efficient administration route than oral delivery. Following inhalation, a larger fraction of the active parent CBD circulates in the blood compared with the inactive metabolite. Additionally, these data show that inhalation delivery has the potential to reduce the concerns of hepatotoxicity associated with oral CBD administration. CBD absorbed from the gastrointestinal tract goes directly to the liver, while CBD absorbed through the lung bypasses first-pass hepatic metabolism.
The oral and inhaled dry powder CBD formulations were generally safe and well-tolerated following a single administration. A few patients who received the DPI CBD formulation experienced a dry, throat-clearing cough following inhalation, not considered an AE by the investigator, that was transient and resolved; this was observed in other studies using the FDKP excipient in patients naïve to dry-powder inhalers.16 Although one participant in the DPI CBD group experienced mild laboratory abnormalities, these were considered unrelated to the study treatment because the participant had engaged in strenuous weight lifting immediately prior to the study and the elevations were expected post exercise. Participants in this study reported that neither the oral nor DPI CBD formulations impacted somnolence as measured by the participant-reported Stanford Sleepiness Scale. Two participants who received the DPI formulation did not inhale properly and the powder did not discharge completely from the inhaler; to prevent this issue, additional inhaler instruction and training will be provided in future studies…
