Oral Transmucosal Research Articles

Pharmacokinetics, sedation and hemodynamic changes following the administration of oral transmucosal detomidine gel in cats.

The aim of this study was to describe the pharmacokinetics of oral transmucosal (OTM) detomidine gel in healthy cats and assess its effects on sedation and hemodynamic variables. Eight adult cats weighing 4.12 kg ± 0.72 received 4 mg/m2 detomidine gel onto the buccal mucosa. Level of sedation, heart rate (HR), blood pressure (BP) and respiratory rate (f R) were assessed at predetermined intervals following administration. Blood samples for plasma detomidine concentrations and venous blood gas variables were collected from a medial saphenous catheter. Plasma detomidine concentrations were analyzed using ultra-high-pressure liquid chromatography with mass spectrometry detection, and pharmacokinetic estimates were obtained with compartmental methods. Data were analyzed using ANOVA and paired t-test or appropriate non-parametric tests. Sedation occurred in all cats, and was increased from baseline at 30 mins (P <0.001). Decreases in HR occurred from 15-60 mins, ranging from 140 to 165 beats per min (P <0.001). Blood glucose increased from 101 ± 12 mg/dl to 168 ± 27.3 mg/dl at 60 mins (P = 0.004). Systolic blood pressure decreased from baseline (139 ± 14.8 mmHg) to 103 ± 23.0 mmHg at 60 mins (P = 0.023). All changes abated by 120 mins. Emesis occurred in 7/7 cats within 2 mins of gel administration. Geometric mean (coefficient of variation) for clearance was 220.7 ml/min/kg (35.3 ml/min/kg), volume of distribution was 14.9 l/kg (39.9 l/kg) (both a function of bioavailability) and elimination half-life was 46.9 mins (16.0 mins). Maximum plasma concentrations of 10.5 ng/ml (35.5 ng/ml) detomidine occurred at 36.9 mins (21.5 mins). OTM detomidine gel produced moderate sedation with minimal undesirable side effects in healthy cats, although emesis occurred in all cats. The pharmacokinetic profile supports short-term, minimally invasive sedation in this species. Further studies are warranted to assess its safety and feasibility for use in debilitated cats, or prior to general anesthesia.

Prolonged oral transmucosal delivery of highly lipophilic drug cannabidiol.

Delivery of drugs through oral mucosa enables bypass of the gastrointestinal tract and "first pass" metabolism in the liver and the gut. Thus, a higher and less variable bioavailability can be obtained. Mechanisms of this administration route for cannabidiol were investigated in the current research in pigs. Results show that cannabidiol has substantially low permeability rate over 8h through oral mucosa and accumulates significantly within it. Furthermore, following the removal of the delivery device, residual prolongation of release from the oral mucosa into systemic blood circulation continues for several hours. This method of delivery enabled acquisition of clinically relevant plasma levels of cannabidiol. The absorption profile indicates that cannabidiol, as well as other lipophilic molecules, should be delivered through oral mucosa for systemic absorption from a device that conceals the drug and prevents its washout by the saliva flow and subsequent ingestion into gastrointestinal tract.

Hypoglycemia after Bariatric Surgery in Mice and Optimal Dosage and Efficacy of Glucose Supplementation.

The Roux-en-Y Gastric Bypass (RYGB) mouse model is a vital tool for studying the pathophysiology of bariatric surgery and contributes greatly to research on obesity and diabetes. However, complications including postsurgical hypoglycemia can have profoundly negative effects. Unlike in humans, blood glucose (BG) is not typically managed in postoperative rodents, despite their critical role as translational models; without this management, rodents can experience hypoglycemia, potentially impairing wound healing, decreasing survivability, complicating interpretation of research data, and limiting translational utility. In this project, we sought to identify an optimal method for minimally invasive administration of dextrose in C57BL/6N (n = 16; 8 male, 8 female) mice. To do so, we characterized BG pharmacokinetic profiles after subcutaneous and oral-transmucosal (OTM) administration of dextrose. Compared with OTM dosage, the subcutaneous route provided more consistent and reliable delivery of glucose and did not cause significant adverse reactions. We then evaluated the frequency of hypoglycemic events after RYGB in C57BL/6N mice (n = 16; 8 male, 8 female) and the effects of subcutaneous dextrose supplementation on morbidity and mortality. BG measurement and behavioral pain assessment (grimace test) were performed for 3 d after surgery. Hypoglycemic (BG ≤ 60 mg/dL) animals were assigned to dose (5% dextrose SC) or no-dose treatment groups. Nearly all (87%) mice became hypoglycemic; 2 of these mice died. No significant intergroup difference in grimace score or mortality was detected. Overall, our results demonstrate that hypoglycemia is a frequent adverse event after RYGB in mice and that subcutaneous injection of dextrose is a safe and effective way to manage hypoglycemia. Further studies are necessary to optimize the intervention threshold and optimal dosage; regardless, we recommend glycemic management after RYGB surgery in mice.

Physiologically Based Pharmacokinetic Modeling to Understand the Absorption of Risperidone Orodispersible Film.

ObjectiveThe aim of the present study was to investigate the absorption routes as well as the potential application of the oral transmucosal delivery of risperidone orodispersible film (ODF) using physiologically based pharmacokinetic modeling.MethodsThe pharmacokinetic study after intragastric (i.g.), supralingual, and sublingual administration of risperidone ODF was conducted in Beagle dogs. Then a mechanic absorption model which combined Oral Cavity Compartment Absorption and Transit (OCCAT) model with Advanced Compartment Absorption and Transit (ACAT) model for predicting the absorption routes of risperidone ODF in vivo was constructed using GastroPlus™. A sensitivity analysis was performed to investigate the impact of oral residence time on the in vivo absorption of risperidone ODF. Based on the fraction of intraoral absorption, the potential of the oral transmucosal delivery of risperidone were predicted.ResultsThere were no statistical differences in the AUC0–t (P = 0.4327), AUC0-∞ (P = 0.3278), Cmax (P = 0.0531), and Tmax (P = 0.2775) values among i.g., supralingual, and sublingual administration of risperidone ODF in Beagle dogs. The predicted absorption percentage via oral mucosa at oral residence time of 2 min, 5 min, and 10 min was 7.0%, 11.4%, and 19.5%, respectively. No obvious difference was observed for the bioavailability of risperidone ODF within 10 min of oral residence time. The PBPK absorption model for risperidone could be simplified to include ACAT model solely. ConclusionThe main absorption route for risperidone ODF was the gastrointestine. The absorption percentage via oral mucosa was almost negligible due to the physicochemical properties of risperidone although ODF dissolved completely in the oral cavity of Beagle dogs within 2 min.

Pharmacokinetics of buprenorphine after intravenous and oral transmucosal administration in guinea pigs (Cavia porcellus).

OBJECTIVE To determine pharmacokinetics and sedative effects of buprenorphine after IV and oral transmucosal (OTM) administration in guinea pigs. ANIMALS 14 male guinea pigs (6 adults for preliminary experiment; eight 8 to 11-week-old animals for primary study). PROCEDURES A preliminary experiment was conducted to determine an appropriate buprenorphine dose. In the primary study, buprenorphine (0.2 mg/kg) was administered IV or OTM, and blood samples were obtained. The pH of the oral cavity was measured before OTM administration. Sedation was scored for 6 hours on a scale of 0 to 3 (0 = no sedation and 3 = heavy sedation). After a 7-day washout period, procedures were repeated in a crossover manner. Plasma buprenorphine concentration was quantified, and data were analyzed with a noncompartmental pharmacokinetic approach. RESULTS Mean peak plasma buprenorphine concentrations were 46.7 and 2.4 ng/mL after IV and OTM administration, respectively. Mean time to maximum plasma buprenorphine concentration was 1.5 and 71.2 minutes, and mean terminal half-life was 184.9 and 173.0 minutes for IV and OTM administration, respectively. There was a range of sedation effects (0 to 2) for both routes of administration, which resolved within the 6-hour time frame. CONCLUSIONS AND CLINICAL RELEVANCE On the basis of pharmacokinetic parameters for this study, buprenorphine at 0.2 mg/kg may be administered IV every 7 hours or OTM every 4 hours to maintain a target plasma concentration of 1 ng/mL. Further studies are needed to evaluate administration of multiple doses and sedative effects in guinea pigs with signs of pain.

Bioavailability of two oral fentanyl transmucosal formulations in healthy volunteers: and open-label, crossover, randomised study

Bioavailability of two oral fentanyl transmucosal formulations in healthy volunteers: and open-label, crossover, randomised study

Transmucosal fentanyl administration: sublingual, buccal, nasal - all the same? Treatment of breakthrough cancer pain

Transient exacerbation of pain in cancer patients (breakthrough cancer pain, BTCP) despite adequately controlled background pain should be regarded as an independent disease and receive targeted treatment. The opioid of choice is fentanyl, a rapid onset and highly potent WHO category III analgesic. Fentanyl has a strong first pass effect when administered orally and resorbed enterally, however it is well suited for transmucosal administration, e.g. on the oral or nasal mucosa. Seven different preparations of rapid onset fentanyl for transmucosal administration via various administration pathways are currently available in Germany. The aim of this review article was to determine which patient can benefit most from which forms of administration. Since there are hardly any direct comparisons of administration forms among each other, meta-analyses and reviews were included in the assessment. Tablets with an applicator (lozenge), sublingual and buccal tablets, as well as a buccal film are available for the oral transmucosal administration of fentanyl; there is an aqueous fentanyl nasal spray and a pectin-rich nasal spray for nasal transmucosal administration. The individual preparations differ considerably with regard to their pharmacological (e.g. bioavailability, cmax and tmax) and patient-relevant parameters (e.g. onset of action, potency and duration of effect). Fentanyl nasal spray is superior to the other forms of administration in terms of rapid onset of action and clinically relevant pain reduction and can thus be recommended as a treatment option for rapidly evolving and/or spontaneously occurring breakthrough cancer pain.

Effect of Buprenorphine Weekly Depot (CAM2038) and Hydromorphone Blockade in Individuals With Opioid Use Disorder

Buprenorphine is an efficacious, widely used treatment for opioid use disorder (OUD). Daily oral transmucosal formulations can be associated with misuse, diversion, and nonadherence; these limitations may be obviated by a sustained release formulation. To evaluate the ability of a novel, weekly, subcutaneous buprenorphine depot formulation, CAM2038, to block euphorigenic opioid effects and suppress opioid withdrawal in non-treatment-seeking individuals with OUD. This multisite, double-blind, randomized within-patient study was conducted at 3 controlled inpatient research facilities. It involved 47 adults with DSM-V moderate-to-severe OUD. The study was conducted from October 12, 2015 (first patient enrolled), to April 21, 2016 (last patient visit). A total of five 3-day test sessions evaluated the response to hydromorphone (0, 6, and 18 mg intramuscular in random order; 1 dose/session/day). After the first 3-day session (ie, qualification phase), participants were randomized to either CAM2038 weekly at 24 mg (n = 22) or 32 mg (n = 25); the assigned CAM2038 dose was given twice, 1 week apart (day 0 and 7). Four sets of sessions were conducted after randomization (days 1-3, 4-6, 8-10, and 11-13). The primary end point was maximum rating on the visual analog scale for drug liking. Secondary end points included other visual analog scale (eg, high and desire to use), opioid withdrawal scales, and physiological and pharmacokinetic outcomes. A total of 46 of 47 randomized participants (mean [SD] age, 35.5 [9] years; 76% male [n = 35]) completed the study. Both weekly CAM2038 doses produced immediate and sustained blockade of hydromorphone effects (liking maximum effect, CAM2038, 24 mg: effect size, 0.813; P < .001, and CAM2038, 32 mg: effect size, 0.753; P < .001) and suppression of withdrawal (Clinical Opiate Withdrawal Scale, CAM2038, 24 mg: effect size, 0.617; P < .001, and CAM2038, 32 mg: effect size, 0.751; P < .001). CAM2038 produces a rapid initial rise of buprenorphine in plasma with maximum concentration around 24 hours, with an apparent half-life of 4 to 5 days and approximately 50% accumulation of trough concentration from first to second dose (trough concentration = 0.822 and 1.23 ng/mL for weeks 1 and 2, respectively, with 24 mg; trough concentration = 0.993 and 1.47 ng/mL for weeks 1 and 2, respectively, with 32 mg). CAM2038 weekly, 24 and 32 mg, was safely tolerated and produced immediate and sustained opioid blockade and withdrawal suppression. The results support the use of this depot formulation for treatment initiation and stabilization of patients with OUD, with the further benefit of obviating the risk for misuse and diversion of daily buprenorphine while retaining its therapeutic benefits. Clinicaltrials.gov Identifier: NCT02611752.

Self-Nanoemulsifying Lyophilized Tablets for Flash Oral Transmucosal Delivery of Vitamin K: Development and Clinical Evaluation

Owing to limited solubility, vitamin K undergoes low bioavailability with large inter-individual variability after oral administration. This article aimed to prepare self-nanoemulsifying lyophilized tablets (SNELTs) for the flash oral transmucosal delivery of vitamin K. Twenty-one formulae of vitamin K self-nanoemulsifying drug delivery systems (SNEDDS) were prepared using different concentrations of vitamin K, Labrasol, and Transcutol according to mixture design. The SNEDDS was loaded on porous carriers and formulated as lyophilized tablets. The release profile and the pharmacokinetic parameters of vitamin K SNELTs were evaluated in comparison with commercial tablets and ampoules on human volunteers. Results revealed that the optimized SNEDDS showed the smallest and most stable nanoemulsion globules. SNELTs were prepared successfully and showed substantial superiority drug release compared with the commercial tablets. Interestingly, SNELTs enhanced both rate and extent of vitamin K absorption as well as relative bioavailability (169.67%) in healthy subjects compared with the commercial tablets. SNELTs revealed promising no significant difference in the area under the curve compared with the commercial intramuscular injection. SNELTs enhanced dissolution and bioavailability that expected to have the strong impact on the efficiency of vitamin K in the prophylaxis and treatment of bleeding disorders in patients with hepatic dysfunction.

A mini-review of non-parenteral clonidine preparations for paediatric sedation.

To provide an overview of non-parenteral clonidine formulations and assess the feasibility of their use for paediatric sedation. A literature search was conducted using electronic databases and a combination of search terms. Forty articles met the inclusion criteria. Publications were grouped into different dosage forms and assessed for their potential application for sedation of children in intensive care. Several routes of clonidine administration have been investigated for numerous indications in children, including perioperative sedation and analgesia. These include oral liquids, tablets, oral transmucosal systems, nasal sprays and rectal suspensions. Conflicting studies on oral transmucosal clonidine formulations suggest that further research is required to fully establish efficacy. Nasal sprays and rectal suspensions have the advantages of rapid onset of action and potential for dose flexibility, but predictable absorption is difficult to obtain. Provided age-appropriate strengths are available, intravenous formulations remain the most predictable in terms of bioavailability and flexible in terms of dose adjustment. However, as with all routes, down-titration is difficult given the long half-life of clonidine. Oral transmucosal systems, nasal sprays and rectal suspensions have potential in a less acute setting, but significant clinical work is required to elucidate a full pharmacokinetic and pharmacodynamic profile.

BUCCAL DRUG DELIVERY SYSTEM : HISTORY AND RECENT DEVELOPMENTS

Abstract Of the various routes of drug delivery, the oral route is most ancient as well as preferred by the patient being convenient to take. However, peroral administration of drugs has short comings such as hepatic first-pass metabolism and enzymatic degradation within the GI-tract which comprehend a hindrance to the absorption of peptides and protein group of drug. The drug absorption takesplace faster as it is in contact with the absorption surface. The drug delivery system helps the drug to remain at the same place of application longer for once or twice daily dosing. For some drugs alternate way of administration results in novel methods of action as opposed to the above said procedure. The characteristics of the oral mucosa as well as physicochemical properties of the drug poses as a hindrance to the oral mucosal administration of some drugs. Commercial availability of drug is restricted, although most of the drugs are qualitatively assessed for oral transmucosal delivery. The clinical benefit produced by an oral transmucosal dosage form is good eventhough the production of this dosage form is expensive. Transmucosal products are the recent drug delivery strategies. Delivery through transmucosal benefits the absorption four times than that of skin. Considering the availability of products, only some drugs are used for oral transmucosal delivery. So new drugs have to be processed and developed inorder to meet the limited transmucosal drug delivery. Present paper intends to emphasis the importance of oral transmucosal drug delivery and also highlights on the latest advancement in the field.

Oral transmucosal delivery of naratriptan

Naratriptan (NAR) is currently used as the hydrochloride salt (NAR.HCl) for the treatment of migraine and is available in tablet dosage forms for oral administration. Buccal drug delivery offers a number of advantages compared with conventional oral delivery including rapid absorption, avoidance of first pass metabolism and improved patient compliance. We have previously prepared and characterised the base form of NAR and shown that it has more favourable properties for buccal delivery compared with NAR.HCl. This study describes the design and evaluation of a range of formulations for oral transmucosal delivery of NAR base. Permeation studies were conducted using excised porcine buccal tissue mounted in Franz cells. Of the neat solvents examined, Transcutol® P (TC) showed the greatest enhancement effects and was the vehicle in which NAR was most soluble. The mechanisms by which TC might promote permeation were further probed using binary systems containing TC with either buffer or Miglyol 812® (MG). Mass balance studies were also conducted for these systems. The permeation of TC as well as NAR was also monitored for TC:MG formulations. Overall, TC appears to promote enhanced membrane permeation of NAR because of its rapid uptake into the buccal tissue. Synergistic enhancement of buccal permeation was observed when TC was combined with MG and this is attributed to the increased thermodynamic activity of NAR in these formulations. Significantly enhanced permeation of NAR was achieved for TC:MG and this was also associated with less TC remaining on the tissue or in the tissue at the end of the experiment. To our knowledge this is the first report where both enhancer and active have been monitored in buccal permeation studies. The findings underline the importance of understanding the fate of vehicle components for rational formulation design of buccal delivery systems.

Pharmacokinetics of detomidine following intravenous or oral-transmucosal administration and sedative effects of the oral-transmucosal treatment in dogs.

To determine the pharmacokinetics of detomidine hydrochloride administered IV (as an injectable formulation) or by the oral-transmucosal (OTM) route (as a gel) and assess sedative effects of the OTM treatment in healthy dogs. 12 healthy adult dogs. In phase 1, detomidine was administered by IV (0.5 mg/m(2)) or OTM (1 mg/m(2)) routes to 6 dogs. After a 24-hour washout period, each dog received the alternate treatment. Blood samples were collected for quantification via liquid chromatography with mass spectrometry and pharmacokinetic analysis. In phase 2, 6 dogs received dexmedetomidine IV (0.125 mg/m(2)) or detomidine gel by OTM administration (0.5 mg/m(2)), and sedation was measured by a blinded observer using 2 standardized sedation scales while dogs underwent jugular catheter placement. After a l-week washout period, each dog received the alternate treatment. Median maximum concentration, time to maximum concentration, and bioavailability for detomidine gel following OTM administration were 7.03 ng/mL, 1.00 hour, and 34.52%, respectively; harmonic mean elimination half-life was 0.63 hours. All dogs were sedated and became laterally recumbent with phase 1 treatments. In phase 2, median global sedation score following OTM administration of detomidine gel was significantly lower (indicating a lesser degree of sedation) than that following IV dexmedetomidine treatment; however, total sedation score during jugular vein catheterization did not differ between treatments. The gel was subjectively easy to administer, and systemic absorption was sufficient for sedation. Detomidine gel administered by the OTM route provided sedation suitable for a short, minimally invasive procedure in healthy dogs.

Comparison of morphine, ketoprofen and Arnica montana 6x and 30x per oral transmucosal or subcutaneous route for control of postoperative pain in cats subjected to hysterectomy with bilateral salpingo-oophorectomy

ABSTRACT: The postoperative analgesic effect of Arnica montana (Arnica) was compared to morphine and ketoprofen in 50 cats following hysterectomy with bilateral salpingo-oophorectomy (HSO). Cats were randomly allocated to five groups (n=10) and were treated 30 minutes before surgery and over 72 hours with 1ml of Arnica 30x per subcutaneous (SC) route (GA30SC); Arnica 30x per oral transmucosal route (P.O.) (GA30PO); Arnica 6x P.O. (GA6PO); morphine 0.1mg kg-1 SC (GM) SID or ketoprofen 2mg kg-1 SC (GK) before and 1mg kg-1 after surgery. Sedation and postoperative pain were assessed by means of a dynamic and interactive visual analogue scale (DIVAS) and variable count scale (VCS) and hyperalgesia using an esthesiometer. Whenever the VAS and VCS scores attained 33% of the maximum value, rescue analgesia was performed with morphine 0.3mg kg-1 per the intramuscular (IM) route. Other variables assessed were vomiting, defecation, urination, body weight and wound healing. Vomiting only occurred in animals treated with morphine. The groups did not differ in defecation, urination, body weight or wound healing. Hyperalgesia was detected only on the occasions that the criterion for rescue analgesia was met. One animal in GK and one in GM required rescue analgesia, differing from groups GA30SC, GA30PO and GA6PO, in which 4, 4 and 5 animals, respectively, required rescue analgesia. It can be concluded that ketoprofen and morphine were more efficacious than Arnica and that there was no difference among the various potencies and routes of administration of Arnica for postoperative analgesia in cats undergoing HSO.

Feasibility of a Comfort Care Protocol Using Oral Transmucosal Medication Delivery in a Palliative Neonatal Population.

The oral transmucosal (OTM) route for administration of comfort medication in infants at the end-of-life has long been favored by our pediatric palliative care team but has rarely been described in the literature. To determine the feasibility of implementing a standardized comfort care protocol using OTM medications in dying neonates. A comfort protocol prescribing medication by the OTM route and standardized assessment were established. Each infant included in the study was assessed with the Neonatal Pain, Agitation, and Sedation Scale (N-PASS). Caretakers' satisfaction was assessed using a questionnaire. The feasibility of implementing the protocol was determined by the proportion of assessments done when required, the rate of termination of the protocol, and the feedback from nurses using the protocol. Twelve patients were enrolled. Regular evaluations were performed 85% of the time. When the medication was given as needed, 71% of cases were evaluated before versus 63% when regular doses were given. The as-needed doses were followed by an assessment 30 minutes later in 49% of cases and in 41%, 60 minutes later, for a total of 64% in the hour after medication administration. The protocol was discontinued only for two patients who were discharged to continue end-of-life care at home. There were no significant adverse events reported. Finally, 17 of 18 nurses said they would recommend this protocol to other institutions. In the context of neonatal palliative care, the implementation of a standardized protocol for administration of drugs by the OTM route is feasible and safe. However, in the context of this study, adherence was limited because of too-frequent evaluations and misunderstanding of the protocol.

Pharmacokinetics of Alternative Administration Routes of Melatonin: A Systematic Review.

Melatonin is traditionally administered orally but has a poor and variable bioavailability. This study aims to present an overview of studies investigating the pharmacokinetics of alternative administration routes of melatonin. A systematic literature search was performed and included experimental or clinical studies, investigating pharmacokinetics of alternative administration routes of melatonin in vivo. Alternative administration routes were defined as all administration routes except oral and intravenous. 10 studies were included in the review. Intranasal administration exhibited a quick absorption rate and high bioavailability. Transdermal administration displayed a variable absorption rate and possible deposition of melatonin in the skin. Oral transmucosal administration of melatonin exhibited a high plasma concentration compared to oral administration. Subcutaneous injection of melatonin displayed a rapid absorption rate compared to oral administration. Intranasal administration of melatonin has a large potential, and more research in humans is warranted. Transdermal application of melatonin has a possible use in a local application, due to slow absorption and deposition in the skin. Oral transmucosal administration may potentially be a clinically relevant due to avoiding first-pass metabolism. Subcutaneous injection of melatonin did not document any advantages compared to other administration routes.

Oral Transmucosal Delivery for Improved Drug Bioavailability and Patient Compliance

Oral Transmucosal Delivery for Improved Drug Bioavailability and Patient Compliance

An Overview on Fast Dissolving Oral Films

Research and developments in oral drug delivery has evolved to changeover of solid dosage forms from conventional solid tablets/capsules to mouth dissolving drug delivery system (MDDS). Intension behind the development of MDDS was to provide the patients with more conventional means of taking their medication. But in MDDS, dissolution of drug in saliva offers the oral transmucosal absorption of the drug to reach to the systemic circulation. Concept of orotransmucosal drug delivery results into various dosage forms which allows orotransmucosal absorption of the drug. Oral strip is the thin film fabricated using hydrophilic polymers that rapidly dissolves beneath the tongue or in buccal cavity and dissolved drug gets absorbed through the oral mucosal surface to reach to the systemic circulation. Here in this review, formulation consideration, manufacturing, physical evaluation of oral films have been discussed.

Pharmacokinetics of oral transmucosal and intramuscular dexmedetomidine combined with buprenorphine in cats.

Plasma concentrations and pharmacokinetics of dexmedetomidine and buprenorphine after oral transmucosal (OTM) and intramuscular (i.m.) administration of their combination in healthy adult cats were compared. According to a crossover protocol (1-month washout), a combination of dexmedetomidine (40μg/kg) and buprenorphine (20μg/kg) was given OTM (buccal cavity) or i.m. (quadriceps muscle) in six female neutered cats. Plasma samples were collected through a jugular catheter during a 24-h period. Plasma dexmedetomidine and buprenorphine concentrations were determined by liquid chromatography-tandem mass spectrometry. Plasma concentration-time data were fitted to compartmental models. For dexmedetomidine and buprenorphine, the area under the plasma concentration-time curve (AUC) and the maximum plasma concentrations (Cmax ) were significantly lower following OTM than following i.m. administration. For buprenorphine, time to reach Cmax was also significantly longer after OTM administration than after i.m. injection. Data suggested that dexmedetomidine (40μg/kg) combined with buprenorphine (20μg/kg) is not as well absorbed from the buccal mucosa site as from the intramuscular injection site.

Oral transmucosal drug delivery--current status and future prospects.

Oral transmucosal drug delivery (OTDD) dosage forms have been available since the 1980s. In contrast to the number of actives currently delivered locally to the oral cavity, the number delivered as buccal or sublingual formulations remains relatively low. This is surprising in view of the advantages associated with OTDD, compared with conventional oral drug delivery. This review examines a number of aspects related to OTDD including the anatomy of the oral cavity, models currently used to study OTDD, as well as commercially available formulations and emerging technologies. The limitations of current methodologies to study OTDD are considered as well as recent publications and new approaches which have advanced our understanding of this route of drug delivery.