The Experts below are selected from a list of 6 Experts worldwide ranked by ideXlab platform
K. Patel Nibha - One of the best experts on this subject based on the ideXlab platform.
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An Overview on: Sublingual Route for Systemic Drug Delivery
2020Co-Authors: K. Patel NibhaAbstract:Oral mucosal Drug delivery is an alternative and promising method of systemic Drug delivery which offers several advantages. Sublingual literally meaning is ''under the tongue'', administrating substance via mouth in such a way that the substance is rapidly absorbed via blood vessels under tongue. Sublingual route offers advantages such as bypasses hepatic first pass metabolic process which gives better bioavailability, rapid onset of action, patient compliance , self-medicated. Dysphagia (difficulty in swallowing) is common among in all ages of people and more in pediatric, geriatric, psychiatric patients. In terms of permeability, Sublingual area of oral cavity is more permeable than buccal area which is in turn is more permeable than palatal area. Different techniques are used to formulate the Sublingual dosage forms. Sublingual Drug Administration is applied in field of cardiovascular Drugs, steroids, enzymes and some barbiturates. This review highlights advantages, disadvantages, different Sublingual formulation such as tablets and films, evaluation.
Peter A. Crooks - One of the best experts on this subject based on the ideXlab platform.
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Development of a GC-MS assay for the determination of fentanyl pharmacokinetics in rabbit plasma after Sublingual spray delivery.
Aaps Journal, 2008Co-Authors: Ahmad H. Malkawi, Abeer M. Al-ghananeem, Peter A. CrooksAbstract:Fentanyl (N-phenyl-N-(1-(2-phenylethyl)4-piperidinyl)propanamide) (Fig. 1), is a potent synthetic opioid agent widely used for surgical analgesia and sedation. Fentanyl is approximately 200 times more potent than morphine and has a quick onset (1–2 min) and short duration of action (30–60 min; 1). Sufentanil, a structurally related compound, is about five to ten times more potent than fentanyl, but has an even shorter duration of action (2). Fentanyl has a selective and potent effect on mu opioid receptors, and is used extensively in the treatment of breakthrough pain (3), which is a transitory exacerbation of pain experienced by a patient who has relatively stable and adequately controlled baseline pain (4). Fig. 1 Chemical structures of fentanyl and sufentanil A rapid onset of pharmacological effect is often desired for some Drugs, especially those used in the treatment of acute disorders. This can effectively be achieved by parenteral Administration. However, this route may not always be the most convenient for the patient. Therefore, there is growing interest in developing new, reliable, and convenient non-parenteral dosage forms utilizing routes of Administration where a rapidly dissolved Drug is immediately absorbed into the systemic circulation. Although conventional oral tablet formulations are generally the first choice for Drug Administration, because of the relative ease of production and usage, some Drugs undergo significant first pass metabolism in the gastrointestinal tract and the liver. In addition, oral tablet or solution Administration of analgesics (i.e. fentanyl) is not considered optimal for management of moderate to severe acute pain or breakthrough pain, principally because of the insufficient intrinsic activity and prolong time-to-peak effect (5). Therefore, there is a growing need for novel dosage forms that can effectively deliver fentanyl in a timely manner, and that have the capability of affording dose titration based on patient need. There has been much interest expressed in the use of oral cavity membranes as sites of Drug Administration (6,7). Oral mucosal delivery, especially that utilizing the Sublingual mucosa as an absorption site, is a promising Drug delivery route which promotes rapid absorption and high bioavailability, with a subsequent, almost immediate onset of pharmacological effect (8). These advantages are the result of the highly vascularized oral mucosa, through which Drugs enter the systemic circulation directly, by-passing the gastrointestinal tract and first pass metabolism in the liver (9). Various in vivo models for intra-oral Drug delivery studies have been evaluated. Rabbit and dog are generally regarded as the most suitable animal models for such studies, since the oral cavities of both animals are histologically similar to that of man (10). Sublingual Drug Administration has been applied to a number of Drugs, including scopolamine, tetrahydrocannabinol, and oxycodone (11–13). All opioid Drugs are absorbed Sublingually to some extent; and fentanyl is particularly well absorbed via this route (14). As the citrate salt, fentanyl is sparingly soluble in water and highly lipophilic, and is expected to be rapidly absorbed Sublingually, because of its ease of permeation through mucous membranes (15). Currently, for the treatment of breakthrough pain, fentanyl is marketed in the form of an injectable dosage form, which has always suffered from issues of patient compliance. Fentanyl citrate has also been developed as a solid intra-oral formulation in shape of a lollipop. This formulation was designed for oral transmucosal Administration in children, to allow rapid absorption of the Drug from the oral cavity. However, it was found that a large proportion of the Drug is swallowed using this delivery system (16). Fentanyl is also administered through the Transdermal Therapeutic Fentanyl-System (TTS-F), which allows for the delivery of a continued and sustained titratable amount of fentanyl without the inconvenience of the typical 24 h Administration of other analgesics. Although incidences of respiratory depression have led to TTS-F being contraindicated for postoperative analgesia, this route of delivery is currently in Phase III clinical trials for treatment of nociceptive, neuropathic and chronic moderate to severe pain, in a variety of settings (17). Several analytical methods have been employed to measure fentanyl in biological samples, including HPLC/UV (18,19), radioimmunoassay (20–22), and GC-MS (23–28) methodologies. However, many HPLC methods lack the sensitivity required for application in pharmacokinetic studies, which often involve long blood sampling times and/or small does of fentanyl. Also, immunoassays tend to suffer from cross-reactivity, and radioanalytical techniques are expensive and not always amenable to human studies. Mass spectrometric methods LC-MS have been also reported (29, 30). GC-MS in the electron impact ionization (EI) mode is one of the most commonly used techniques in Drug analysis, and although some GC-MS methods for analyzing fentanyl have been reported, they are time-consuming, due to the number of purification and derivatization steps employed. Nevertheless, GC-MS offers the best sensitivity of the currently available methods for determining fentanyl in biological fluids when utilizing the Single Ion Monitoring (SIM) mode of operation, which affords unparalleled specificity. The main objective of this current study is two-fold; to develop a simple and sensitive GC-MS-EI method for the quantitation of nanogram levels of fentanyl in support of preclinical pharmacokinetic studies and then to determine the extent of fentanyl absorption from Sublingual tissue and distribution to the general circulation compared to intravenous Administration in the rabbit.
Ahmad H. Malkawi - One of the best experts on this subject based on the ideXlab platform.
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Development of a GC-MS assay for the determination of fentanyl pharmacokinetics in rabbit plasma after Sublingual spray delivery.
Aaps Journal, 2008Co-Authors: Ahmad H. Malkawi, Abeer M. Al-ghananeem, Peter A. CrooksAbstract:Fentanyl (N-phenyl-N-(1-(2-phenylethyl)4-piperidinyl)propanamide) (Fig. 1), is a potent synthetic opioid agent widely used for surgical analgesia and sedation. Fentanyl is approximately 200 times more potent than morphine and has a quick onset (1–2 min) and short duration of action (30–60 min; 1). Sufentanil, a structurally related compound, is about five to ten times more potent than fentanyl, but has an even shorter duration of action (2). Fentanyl has a selective and potent effect on mu opioid receptors, and is used extensively in the treatment of breakthrough pain (3), which is a transitory exacerbation of pain experienced by a patient who has relatively stable and adequately controlled baseline pain (4). Fig. 1 Chemical structures of fentanyl and sufentanil A rapid onset of pharmacological effect is often desired for some Drugs, especially those used in the treatment of acute disorders. This can effectively be achieved by parenteral Administration. However, this route may not always be the most convenient for the patient. Therefore, there is growing interest in developing new, reliable, and convenient non-parenteral dosage forms utilizing routes of Administration where a rapidly dissolved Drug is immediately absorbed into the systemic circulation. Although conventional oral tablet formulations are generally the first choice for Drug Administration, because of the relative ease of production and usage, some Drugs undergo significant first pass metabolism in the gastrointestinal tract and the liver. In addition, oral tablet or solution Administration of analgesics (i.e. fentanyl) is not considered optimal for management of moderate to severe acute pain or breakthrough pain, principally because of the insufficient intrinsic activity and prolong time-to-peak effect (5). Therefore, there is a growing need for novel dosage forms that can effectively deliver fentanyl in a timely manner, and that have the capability of affording dose titration based on patient need. There has been much interest expressed in the use of oral cavity membranes as sites of Drug Administration (6,7). Oral mucosal delivery, especially that utilizing the Sublingual mucosa as an absorption site, is a promising Drug delivery route which promotes rapid absorption and high bioavailability, with a subsequent, almost immediate onset of pharmacological effect (8). These advantages are the result of the highly vascularized oral mucosa, through which Drugs enter the systemic circulation directly, by-passing the gastrointestinal tract and first pass metabolism in the liver (9). Various in vivo models for intra-oral Drug delivery studies have been evaluated. Rabbit and dog are generally regarded as the most suitable animal models for such studies, since the oral cavities of both animals are histologically similar to that of man (10). Sublingual Drug Administration has been applied to a number of Drugs, including scopolamine, tetrahydrocannabinol, and oxycodone (11–13). All opioid Drugs are absorbed Sublingually to some extent; and fentanyl is particularly well absorbed via this route (14). As the citrate salt, fentanyl is sparingly soluble in water and highly lipophilic, and is expected to be rapidly absorbed Sublingually, because of its ease of permeation through mucous membranes (15). Currently, for the treatment of breakthrough pain, fentanyl is marketed in the form of an injectable dosage form, which has always suffered from issues of patient compliance. Fentanyl citrate has also been developed as a solid intra-oral formulation in shape of a lollipop. This formulation was designed for oral transmucosal Administration in children, to allow rapid absorption of the Drug from the oral cavity. However, it was found that a large proportion of the Drug is swallowed using this delivery system (16). Fentanyl is also administered through the Transdermal Therapeutic Fentanyl-System (TTS-F), which allows for the delivery of a continued and sustained titratable amount of fentanyl without the inconvenience of the typical 24 h Administration of other analgesics. Although incidences of respiratory depression have led to TTS-F being contraindicated for postoperative analgesia, this route of delivery is currently in Phase III clinical trials for treatment of nociceptive, neuropathic and chronic moderate to severe pain, in a variety of settings (17). Several analytical methods have been employed to measure fentanyl in biological samples, including HPLC/UV (18,19), radioimmunoassay (20–22), and GC-MS (23–28) methodologies. However, many HPLC methods lack the sensitivity required for application in pharmacokinetic studies, which often involve long blood sampling times and/or small does of fentanyl. Also, immunoassays tend to suffer from cross-reactivity, and radioanalytical techniques are expensive and not always amenable to human studies. Mass spectrometric methods LC-MS have been also reported (29, 30). GC-MS in the electron impact ionization (EI) mode is one of the most commonly used techniques in Drug analysis, and although some GC-MS methods for analyzing fentanyl have been reported, they are time-consuming, due to the number of purification and derivatization steps employed. Nevertheless, GC-MS offers the best sensitivity of the currently available methods for determining fentanyl in biological fluids when utilizing the Single Ion Monitoring (SIM) mode of operation, which affords unparalleled specificity. The main objective of this current study is two-fold; to develop a simple and sensitive GC-MS-EI method for the quantitation of nanogram levels of fentanyl in support of preclinical pharmacokinetic studies and then to determine the extent of fentanyl absorption from Sublingual tissue and distribution to the general circulation compared to intravenous Administration in the rabbit.
Abeer M. Al-ghananeem - One of the best experts on this subject based on the ideXlab platform.
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Development of a GC-MS assay for the determination of fentanyl pharmacokinetics in rabbit plasma after Sublingual spray delivery.
Aaps Journal, 2008Co-Authors: Ahmad H. Malkawi, Abeer M. Al-ghananeem, Peter A. CrooksAbstract:Fentanyl (N-phenyl-N-(1-(2-phenylethyl)4-piperidinyl)propanamide) (Fig. 1), is a potent synthetic opioid agent widely used for surgical analgesia and sedation. Fentanyl is approximately 200 times more potent than morphine and has a quick onset (1–2 min) and short duration of action (30–60 min; 1). Sufentanil, a structurally related compound, is about five to ten times more potent than fentanyl, but has an even shorter duration of action (2). Fentanyl has a selective and potent effect on mu opioid receptors, and is used extensively in the treatment of breakthrough pain (3), which is a transitory exacerbation of pain experienced by a patient who has relatively stable and adequately controlled baseline pain (4). Fig. 1 Chemical structures of fentanyl and sufentanil A rapid onset of pharmacological effect is often desired for some Drugs, especially those used in the treatment of acute disorders. This can effectively be achieved by parenteral Administration. However, this route may not always be the most convenient for the patient. Therefore, there is growing interest in developing new, reliable, and convenient non-parenteral dosage forms utilizing routes of Administration where a rapidly dissolved Drug is immediately absorbed into the systemic circulation. Although conventional oral tablet formulations are generally the first choice for Drug Administration, because of the relative ease of production and usage, some Drugs undergo significant first pass metabolism in the gastrointestinal tract and the liver. In addition, oral tablet or solution Administration of analgesics (i.e. fentanyl) is not considered optimal for management of moderate to severe acute pain or breakthrough pain, principally because of the insufficient intrinsic activity and prolong time-to-peak effect (5). Therefore, there is a growing need for novel dosage forms that can effectively deliver fentanyl in a timely manner, and that have the capability of affording dose titration based on patient need. There has been much interest expressed in the use of oral cavity membranes as sites of Drug Administration (6,7). Oral mucosal delivery, especially that utilizing the Sublingual mucosa as an absorption site, is a promising Drug delivery route which promotes rapid absorption and high bioavailability, with a subsequent, almost immediate onset of pharmacological effect (8). These advantages are the result of the highly vascularized oral mucosa, through which Drugs enter the systemic circulation directly, by-passing the gastrointestinal tract and first pass metabolism in the liver (9). Various in vivo models for intra-oral Drug delivery studies have been evaluated. Rabbit and dog are generally regarded as the most suitable animal models for such studies, since the oral cavities of both animals are histologically similar to that of man (10). Sublingual Drug Administration has been applied to a number of Drugs, including scopolamine, tetrahydrocannabinol, and oxycodone (11–13). All opioid Drugs are absorbed Sublingually to some extent; and fentanyl is particularly well absorbed via this route (14). As the citrate salt, fentanyl is sparingly soluble in water and highly lipophilic, and is expected to be rapidly absorbed Sublingually, because of its ease of permeation through mucous membranes (15). Currently, for the treatment of breakthrough pain, fentanyl is marketed in the form of an injectable dosage form, which has always suffered from issues of patient compliance. Fentanyl citrate has also been developed as a solid intra-oral formulation in shape of a lollipop. This formulation was designed for oral transmucosal Administration in children, to allow rapid absorption of the Drug from the oral cavity. However, it was found that a large proportion of the Drug is swallowed using this delivery system (16). Fentanyl is also administered through the Transdermal Therapeutic Fentanyl-System (TTS-F), which allows for the delivery of a continued and sustained titratable amount of fentanyl without the inconvenience of the typical 24 h Administration of other analgesics. Although incidences of respiratory depression have led to TTS-F being contraindicated for postoperative analgesia, this route of delivery is currently in Phase III clinical trials for treatment of nociceptive, neuropathic and chronic moderate to severe pain, in a variety of settings (17). Several analytical methods have been employed to measure fentanyl in biological samples, including HPLC/UV (18,19), radioimmunoassay (20–22), and GC-MS (23–28) methodologies. However, many HPLC methods lack the sensitivity required for application in pharmacokinetic studies, which often involve long blood sampling times and/or small does of fentanyl. Also, immunoassays tend to suffer from cross-reactivity, and radioanalytical techniques are expensive and not always amenable to human studies. Mass spectrometric methods LC-MS have been also reported (29, 30). GC-MS in the electron impact ionization (EI) mode is one of the most commonly used techniques in Drug analysis, and although some GC-MS methods for analyzing fentanyl have been reported, they are time-consuming, due to the number of purification and derivatization steps employed. Nevertheless, GC-MS offers the best sensitivity of the currently available methods for determining fentanyl in biological fluids when utilizing the Single Ion Monitoring (SIM) mode of operation, which affords unparalleled specificity. The main objective of this current study is two-fold; to develop a simple and sensitive GC-MS-EI method for the quantitation of nanogram levels of fentanyl in support of preclinical pharmacokinetic studies and then to determine the extent of fentanyl absorption from Sublingual tissue and distribution to the general circulation compared to intravenous Administration in the rabbit.
