Effect of high-flow nasal and buccal oxygenation on safe apnea time in children with open mouth: A randomized controlled trial.

BACKGROUND: High-flow nasal oxygenation is reported to prolong duration of apnea while maintaining adequate oxygen saturation with the mouth closed. Also, buccal oxygenation is known to have similar effects in obese adults. We compared the effect of these two methods on prolongation of acceptable apnea time in pediatric patients with their mouth open. METHODS: Thirty-eight patients, aged 0-10 years were randomly allocated to either the high-flow nasal oxygenation group (n = 17) or the buccal oxygenation group (n = 21). After induction of anesthesia including neuromuscular blockade, manual ventilation was initiated until the expiratory oxygen concentration reached 90%. Subsequently, ventilation was paused, and the patient's head was extended, and mouth was opened. The HFNO group received 2 L·min-1·kg-1 of oxygen, and the BO group received 0.5 L·min-1·kg-1 of oxygen. We set a target apnea time according to previous literature. When the apnea time reached the target, we defined the case as "success" in prolongation of safe apnea time and resumed ventilation. When the pulse oximetry decreased to 92% before the target apnea time, it was recorded as "failure" and rescue ventilation was given. RESULTS: The success rate of safe apnea prolongation was 100% in the high-flow nasal oxygenation group compared to 76% in the buccal oxygenation group (p = .04). Oxygen reserve index, end-tidal or transcutaneous carbon dioxide partial pressure, and pulse oximetry did not differ between groups. CONCLUSION: High-flow nasal oxygenation is effective in maintaining appropriate arterial oxygen saturation during apnea even in children with their mouth open and is superior to buccal oxygenation. Buccal oxygenation may be a good alternative when high-flow nasal oxygenation is not available.

Effectiveness of fentanyl buccal soluble film in cancer patients with inadequate breakthrough pain control.

BACKGROUND: Clinical evidence for the rapidity and effectiveness of fentanyl buccal soluble film (FBSF) in reducing pain intensity of breakthrough cancer pain (BTcP) remains inadequate. This study aimed to evaluate the efficacy of FBSF proportional to the around-the-clock (ATC) opioid regimens in rapidly relieving the intensity of BTcP episodes by determining the percentage of patients requiring further dose titration. METHODS: The study procedure included a dose-finding period followed by a 14-day observation period. Pain intensity was recorded with a Numeric Rating Scale (NRS) at onset and 5, 10, 15, and 30 min after FBSF self-administration. Meaningful pain relief was defined as the final NRS score ≤ 3. Satisfaction survey was conducted for each patient after treatment using the Global Satisfaction Scale. RESULTS: A total of 63 BTcP episodes occurred in 30 cancer patients. Only one patient required rescue medication at first BTcP episode and then achieved meaningful pain relief after titrating FBSF by 200 µg. Most BTcP episodes relieved within 10 min. Of 63 BTcP episodes, 30 (47.6%), 46 (73.0%), and 53 (84.1%) relieved within 5, 10, and 15 min after FBSF administration. Only grade 1/2 adverse events were reported, including somnolence, malaise, and dizziness. Of the 63 BTcP episodes, 82.6% were rated as excellent/good satisfaction with FBSF. CONCLUSION: FBSF can be administrated "on demand" by cancer patients at the onset of BTcP, providing rapid analgesia by achieving meaningful pain relief within 10 min. TRIAL REGISTRATION: This study was retrospectively registered 24 December, 2021 at Clinicaltrial.gov (NCT05209906): https://clinicaltrials.gov/study/NCT05209906 .

Buccal versus Vaginal Misoprostol Combined with a Foley Catheter among Individuals with Obesity Undergoing Induction.

OBJECTIVE: Combining pharmacologic agents with mechanical ripening achieves the shortest labor duration, yet there is no clear evidence on route of drug administration in obese individuals. The use of buccal misoprostol has shown greater patient acceptance but remains understudied. Our objective was to evaluate the difference in time to delivery of buccal compared with vaginal misoprostol in combination with a Foley catheter (FC) for induction of labor (IOL) in the obese population. STUDY DESIGN: This was a secondary analysis of a randomized controlled trial comparing identical dosages (25 µg) of buccal and vaginal misoprostol in combination with a FC. The parent trial was an institutional review board-approved, randomized clinical trial conducted from June 2019 through January 2020. Labor management was standardized among participants. Women undergoing IOL at ≥37 weeks with a singleton gestation and cervical dilation ≤2 cm were included. Body mass index (BMI, kg/m2) was stratified. The primary outcome was time to delivery. RESULTS: A total of 215 participants were included. Demographic characteristics were similar between the three groups. Vaginal drug administration achieved a faster median time to delivery than the buccal route among patients with a body mass index greater than or equal to 30 kg/m2 (vaginal misoprostol-FC: 21.3 hours vs. buccal misoprostol-FC: 25.2 hours, p = 0.006). There was no difference in the cesarean delivery rate between the two groups. Furthermore, patients with a BMI greater than or equal to 30 kg/m2 receiving vaginal misoprostol delivered 1.2 times faster than women who received buccal misoprostol after censoring for cesarean delivery and adjusting for parity (hazard ratio: 1.2, 95% confidence interval: 1.1-1.7). There were no significant differences in maternal and neonatal outcomes. CONCLUSION: We found that vaginal misoprostol was superior to buccal misoprostol when combined with a FC among individuals with a BMI greater than or equal to 30 kg/m2. Vaginal misoprostol should be the preferred route of drug administration for term IOL in this population. KEY POINTS: · Vaginal misoprostol was superior to buccal route among patients with obesity.. · There was no difference in the cesarean delivery rate between the two groups.. · Vaginal misoprostol should be the preferred route of administration among patients with obesity..

Fabrication and Characterization of Pectin Films Containing Solid Lipid Nanoparticles for Buccal Delivery of Fluconazole.

Fluconazole (FZ) is a potential antifungal compound for treating superficial and systemic candidiasis. However, the use of conventional oral drug products has some limitations. The development of buccal film may be a potential alternative to oral formulations for FZ delivery. The present study involved the development of novel FZ-loaded solid lipid nanoparticles (FZ-SLNs) in pectin solutions and the investigation of their particle characteristics. The particle sizes of the obtained FZ-SLNs were in the nanoscale range. To produce pectin films with FZ-SLNs, four formulations were selected based on the small particle size of FZ-SLNs and their suitable polydispersity index. The mean particle sizes of all chosen FZ-SLNs formulations did not exceed 131.7 nm, and the mean polydispersity index of each formulation was less than 0.5. The properties of films containing FZ-SLNs were then assessed. The preparation of all FZ-SLN-loaded pectin films provided the mucoadhesive matrices. The evaluation of mechanical properties unveiled the influence of particle size variation in FZ-SLNs on the integrity of the film. The Fourier-transform infrared spectra indicated that hydrogen bonds could potentially form between the pectin-based matrix and the constituents of FZ-SLNs. The differential scanning calorimetry thermogram of each pectin film with FZ-SLNs revealed that the formulation was thermally stable and behaved in a solid state at 37 °C. According to a drug release study, a sustained drug release pattern with a burst in the initial stage for all films may be advantageous for reducing the lag period of drug release. All prepared films with FZ-SLNs provided a sustained release of FZ over 6 h. The films containing FZ-SLNs with a small particle size provided good permeability across the porcine mucosa. All film samples demonstrated antifungal properties. These results suggest the potential utility of pectin films incorporating FZ-SLNs for buccal administration.

Buccal lidocaine mucoadhesive patches for pediatrics' teething pain: overcoming possible hazards of oral gels.

OBJECTIVES: The utilization of pharmaceutical products in pediatric medicine, while established for use in adults, often presents uncertainties due to differences in application for children. The FDA discourages the use of local anesthetic gels, notably lidocaine, for teething pain in pediatrics due to concerns regarding potential adverse effects if inadvertently swallowed excessively. Therefore, significant attention is being directed towards modifying available marketed products to make them suitable for pediatric use. Here, we introduce mucoadhesive patches that not only have an adjusted dose of lidocaine but also feature a controlled release profile to manage teething pain with prolonged effect. This design helps to prevent issues related to gel liquefaction and swallowing, thereby reducing the potential hazardous side effects of lidocaine in the pediatric population. METHODS: The study involved the development of controlled-release lidocaine HCl-loaded pellets forming a matrix for inclusion in mucoadhesive patches. Characterization was performed to ensure prolonged drug release, particularly during overnight use, aiming to improve pediatric patient compliance and enable precise dosing. KEY FINDINGS: The mucoadhesive patches exhibited sustained lidocaine release lasting 24 h, potentially offering overnight relief suitable for pediatric application. The analysis of lidocaine content revealed that the developed patches maintained stable levels compared to doses obtained from commercially available oral gels. This finding implies effective pain control without the need for frequent reapplications, alongside controlled doses that decrease the likelihood of side effects. CONCLUSION: The formulated medicated patches demonstrated consistent lidocaine content, effectively controlled drug release, and consequently, reduced the likelihood of undesired side effects when compared to oral gel administration.

Nanosuspension-Based Repaglinide Fast-Dissolving Buccal Film for Dissolution Enhancement.

Drug solubility and dissolution remain a significant challenge in pharmaceutical formulations. This study aimed to formulate and evaluate repanglinide (RPG) nanosuspension-based buccal fast-dissolving films (BDFs) for dissolution enhancement. RPG nanosuspension was prepared by the antisolvent-precipitation method using multiple hydrophilic polymers, including soluplus®, polyvinyl alcohol, polyvinyl pyrrolidine, poloxamers, and hydroxyl propyl methyl cellulose. The nanosuspension was then directly loaded into BDFs using the solvent casting technique. Twelve formulas were prepared with a particle size range of 81.6-1389 nm and PDI 0.002-1 for the different polymers. Nanosuspensions prepared with soluplus showed a favored mean particle size of 82.6 ± 3.2 nm. The particles were spherical and non-aggregating, as demonstrated by SEM imaging. FTIR showed no interaction between soluplus and RPG. Faster dissolution occurred for the nanosuspension in comparison with pure RPG (complete release vs 60% within 30 min). The nanosuspension was successfully incorporated into BDFs. The optimum film formula showed 28 s disintegration time, and 97.3% RPG released within 10 min. Ex-vivo permeation profiles revealed improved RPG nanosuspension permeation with the cumulative amount of RPG permeated is103.4% ± 10.1 and a flux of 0.00275 mg/cm2/min compared to 39.3% ± 9.57 and a flux of 0.001058 mg/cm2/min for pure RPG. RPG was successfully formulated into nanosuspension that boosted drug dissolution and permeation. The selection of the ultimate NP formula was driven by optimal particle size, distribution, and drug content. Soluplus NPs were shown to be the successful formulations, which were further incorporated into a buccal film. The film was evaluated for ex-vivo permeation, confirming successful RPG formulation with improved performance compared to pure drugs.

Tailored Sticky Solutions: 3D-Printed Miconazole Buccal Films for Pediatric Oral Candidiasis.

In this research, 3D-printed antifungal buccal films (BFs) were manufactured as a potential alternative to commercially available antifungal oral gels addressing key considerations such as ease of manufacturing, convenience of administration, enhanced drug efficacy and suitability of paediatric patients. The fabrication process involved the use of a semi-solid extrusion method to create BFs from zein-Poly-Vinyl-Pyrrolidone (zein-PVP) polymer blend, which served as a carrier for drug (miconazole) and taste enhancers. After manufacturing, it was determined that the disintegration time for all films was less than 10 min. However, these films are designed to adhere to buccal tissue, ensuring sustained drug release. Approximately 80% of the miconazole was released gradually over 2 h from the zein/PVP matrix of the 3D printed films. Moreover, a detailed physicochemical characterization including spectroscopic and thermal methods was conducted to assess solid state and thermal stability of film constituents. Mucoadhesive properties and mechanical evaluation were also studied, while permeability studies revealed the extent to which film-loaded miconazole permeates through buccal tissue compared to commercially available oral gel formulation. Histological evaluation of the treated tissues was followed. Furthermore, in vitro antifungal activity was assessed for the developed films and the commercial oral gel. Finally, films underwent a two-month drug stability test to ascertain the suitability of the BFs for clinical application. The results demonstrate that 3D-printed films are a promising alternative for local administration of miconazole in the oral cavity.

Metoclopramide loaded buccal films for potential treatment of migraine symptoms: in vitro and in vivo study.

OBJECTIVE: Developing mucoadhesive buccal films loaded with metoclopramide for the treatment of migraine-associated vomiting. METHODS: Buccal films were prepared using the solvent casting method. Several tests were conducted, including measurement of film weight, thickness, drug content, moisture uptake, swelling index, and DSC analysis. The bioadhesion properties were also assessed. Furthermore, in vitro release profiles and in human bioavailability were studied. RESULTS: The developed films were transparent, homogeneous, and easy to remove. Film weight and thickness increased with higher drug content. The drug entrapment exceeded 90%. Film weight increased with moisture uptake, and DSC analysis indicated the absence of drug crystallinity. Bioadhesion properties and swelling index decreased with increasing drug content. In vitro release demonstrated that drug release depended on the drug-polymer ratio. The in vivo study showed significant improvements in Tmax (from 1.21 ± 0.33 to 0.50 ± 0.0) and Cmax (from 45.29 ± 14.66 to 63.27 ± 24.85) compared to conventional tablets. CONCLUSION: The prepared mucoadhesive buccal films exhibited the desired characteristics and demonstrated enhanced drug absorption, evidenced by the significantly reduced Tmax and increased Cmax compared to conventional tablets. The results indicate the successful achievement of the study objectives in selecting and designing an effective pharmaceutical dosage form. as cm2.

Fabrication and Characterization of Buccal Film Loaded Self-emulsifying Drug Delivery System containing Lysiphyllum strychnifolium Stem Extracts.

Lysiphyllum strychnifolium has long been used as a popular herbal medicinal plant for treating fever and alcohol intoxication. This study aimed to prepare buccal film for L. strychnifolium stem extracts. These extracts were less soluble in water and were therefore loaded in self-emulsifying systems before being mixed into the film. Astilbin was selected as a chemical marker in L. strychnifolium stem extracts. Firstly, the L. strychnifolium stem extracts were entrapped in the self-emulsifying systems which were designed and optimized based on 32 factorial design. The optimal formulation was 0.60 g of surfactant-co-surfactant mixture (Tween® 80 and polyethylene glycol 400 in the ratio of 7.5:1) and 0.40 g of caprylic/capric triglyceride. Secondly, the optimal self-emulsifying system was loaded in the polymeric film which consisted of polyvinyl alcohol blended with poloxamer 407 using glycerin as a plasticizer. The properties of the prepared buccal film were unchanged, and the film showed an amorphous state, indicating all ingredients might be completely dissolved in the film. The buccal film could be placed in direct contact with the mouth without oral mucosal irritation, and showed a smooth and homogeneous surface with a rough and compact cross-sectional morphology. Astilbin content in the buccal film was 61.39 ± 11.45 µg/cm2. Astilbin was released from the buccal film while the permeation rate was low. The release mechanism was both swelling and diffusion, and followed anomalous or non-Fickian transfer. The permeability coefficient of the cumulative amount of astilbin permeated from buccal film was 1.0192 ± 0.1395 ×10-3 cm/h. Thus, the buccal film can be prepared by using a self-emulsifying system for herbal applications and shows potential as a safe and convenient form of oral drug administration.

Development and Evaluation of Combined Effect Buccal Films for Treatment of Oral Candidiasis.

Buccal film formulations, including antifungal nystatin, anti-inflammatory agent hydrocortisone acetate, and local anesthetic lidocaine hydrochloride for pain relief, were developed. Bioadhesive films were fabricated with hydrophilic polymers, hydroxyethyl cellulose (HEC), and xanthan gum (XG) and dried in the incubator. Textural, swelling, and bioadhesive properties, physicochemical and in vitro release characteristics, and antifungal activities of bioadhesive films were evaluated.Bioadhesive films significantly extended nystatin release by prolonging retention time of the target area formulation while rapidly releasing hydrocortisone acetate and lidocaine HCl, reducing drug administration. The polymer type affected bioadhesion strength and erosion ratio, and XG formulations had more polymer suitability. Consequently, XT-O2 formulation that was prepared with xanthan gum and tween 80, was best for its highest antifungal film activity (20.00 ± 0.07 mm), released nystatin (44.296% ± 1.695), and lowest erosion matrix (36.719% ± 0.249). The selected formulation can be used for compatibility, stability and in vivo studies targeted oral candidiasis infections.

Buccal vs vaginal misoprostol combined with Foley catheter for cervical ripening at term (the BEGIN trial): a randomized controlled trial.

BACKGROUND: Combining pharmacologic agents with mechanical ripening achieves the shortest time to labor; however, there is no clear evidence on route of drug administration. Buccal administration of misoprostol has shown greater patient acceptance but remains understudied. OBJECTIVE: This study aimed to evaluate the difference in time to delivery between buccal and vaginal administration of misoprostol along with a Foley catheter for induction of labor. STUDY DESIGN: The BEGIN trial (buccal vs vaginal misoprostol combined with Foley catheter for cervical ripening at term) was an institutional review board-approved, randomized clinical trial conducted from June 2019 to January 2020 comparing identical doses (25 µg) of buccal misoprostol and vaginal misoprostol along with a Foley catheter for induction of labor. Randomization was stratified by parity. Labor management was standardized among participants. Individuals undergoing induction of labor at ≥37 weeks with a singleton gestation and needing cervical ripening were included. Our primary outcome was time to delivery. Kruskal-Wallis, Pearson chi-squared, and Cox survival analyses with intent-to-treat principles were performed. A sample size of 216 was planned to detect a 4-hour reduction in delivery time. RESULTS: A total of 215 women (108 in the buccal drug administration group and 107 in the vaginal drug administration group) were randomized. The vaginal route of drug administration achieved a faster median time to delivery than the buccal route of drug administration (19.7 hours in the vaginal route vs 24.1 hours in the buccal route; P<.001). A greater percentage of women in the vaginal drug administration group delivered within 24 hours compared with the buccal drug administration group (65% vs 49%; P=.02). There was no difference in the cesarean delivery rate between the 2 groups (17% in the vaginal drug administration group vs 21% in the buccal drug administration group; P=.6). Individuals who received vaginal misoprostol with Foley catheter delivered 2 times faster than women who received buccal misoprostol with Foley catheter after censoring for cesarean delivery and adjusting for parity (hazard ratio, 2.13; 95% confidence interval, 1.44-3.17). There was no significant difference in maternal and neonatal outcomes. CONCLUSION: We found that vaginal administration of misoprostol was superior to buccal administration of misoprostol along with a Foley catheter for induction of labor. Furthermore, vaginal administration of misoprostol resulted in twice the chance of delivering earlier compared with buccal administration of misoprostol with no difference in cesarean delivery rates. Therefore, the vaginal route of administration of misoprostol should be preferred among individuals undergoing a combined pharmacologic and mechanical induction.

Pharmacokinetics and Pharmacodynamics of 3 Doses of Oral-Mucosal Dexmedetomidine Gel for Sedative Premedication in Women Undergoing Modified Radical Mastectomy for Breast Cancer.

BACKGROUND: Buccal dexmedetomidine (DEX) produces adequate preoperative sedation and anxiolysis when used as a premedication. Formulating the drug as a gel decreases oral losses and improves the absorption of buccal DEX. We compared pharmacokinetic and pharmacodynamic properties of 3 doses of buccal DEX gel formulated in our pharmaceutical laboratory for sedative premedication in women undergoing modified radical mastectomy for breast cancer. METHODS: Thirty-six patients enrolled in 3 groups (n = 12) to receive buccal DEX gel 30 minutes before surgery at 0.5 µg/kg (DEX 0.5 group), 0.75 µg/kg (DEX 0.75 group), or 1 µg/kg (DEX 1 group). Assessments included plasma concentrations of DEX, and pharmacokinetic variables calculated with noncompartmental methods, sedative, hemodynamic and analgesic effects, and adverse effects. RESULTS: The median time to reach peak serum concentration of DEX (Tmax) was significantly shorter in patients who received 1 µg/kg (60 minutes) compared with those who received 0.5 µg/kg (120 minutes; P = .003) and 0.75 µg/kg (120 minutes; P = .004). The median (first quartile-third quartile) peak concentration of DEX (maximum plasma concentration [Cmax]) in plasma was 0.35 ng/mL (0.31-0.49), 0.37 ng/mL (0.34-0.40), and 0.54 ng/mL (0.45-0.61) in DEX 0.5, DEX 0.75, and DEX 1 groups (P = .082). The 3 doses did not produce preoperative sedation. The 1 µg/kg buccal DEX gel produced early postoperative sedation and lower intraoperative and postoperative heart rate values. Postoperative analgesia was evident in the 3 doses in a dose-dependent manner with no adverse effects. CONCLUSIONS: Provided that it is administered 60-120 minutes before surgery, sublingual administration of DEX formulated as an oral-mucosal gel may provide a safe and practical means of sedative premedication in adults.

The role of fentanyl in the treatment of breakthrough cancer pain: Different biotechnologies, different results and different drug costs.

The aim of this paper was to assess the drug costs of the different biotechnologies (intranasal fentanyl spray (INFS), oral transmucosal fentanyl citrate (OTFC) and fentanyl buccal tablet (FBT)) in the treatment of breakthrough cancer pain (BTCP). We have calculated the mean drug costs (expressed in euros (€)) for patients treated for BTCP. INFS resulted the less expensive towards OTFC and FBT, with 697 440 €versus (vs.) 809 552 €vs. 779 662 €every 100 patients treated for BTCP, respectively. In conclusion, combining drug costs of different biotechnologies (INFS, OTFC and FBT) with the measure of efficacy represented by the reduction of BTCP avoided (incremental cost-effectiveness ratio, ICER), INFS resulted in better cost-effectiveness.

Development and optimization of tibezonium iodide and lignocaine hydrochloride containing novel mucoadhesive buccal tablets: a pharmacokinetic investigation among healthy humans.

OBJECTIVE: It is clinically important to deliver a sustained-release mucoadhesive dosage of local anesthetic and antimicrobial agents for pain control. The current study aimed to develop and evaluate chitosan (CHI) based buccal mucoadhesive delivery for the local release of tibezonium iodide (TBN) and lignocaine hydrochloride (LGN). METHODS: Direct compression technique was employed, aided by other mucoadhesive polymers like hydroxypropylmethylcellulose (HPMC) and sodium alginate (SA) and evaluated for physicochemical and in vivo character. RESULTS: Fourier transform infrared spectral analysis (FTIR), powdered X-ray diffraction (XRPD), and differential scanning calorimetry (DSC) absence of physical interaction between ingredients. The physical parameters complied with USP specifications for all formulations. Optimum swellability (551.9%) was offered from formulation TL15, containing 30% SA. The highest ex vivo mucoadhesive strength (24.79 g) and time (18.39 h) was found with TL8. Formulation TL8 also exhibited maximum in vivo residence time (11.37 h). Almost complete drug release at 6 h was possessed by formulation TL5 (HPMC and CHI, 20% each) for TBN (99.98%) and LGN (99.06%). The optimized formulation TL5 exhibited dosage stability up to 6 months at 75% relative humidity and retained drug contents. TL5 was well tolerated by the volunteers with no inflammation, pain or irritation found. Almost 73% of volunteers reported an increase in salivary secretion. The first-order salivary Cmax of TBN and LGN were found as 16.02 and 7.80 µg/mL within 4 h, respectively. CONCLUSION: Therefore, the sustained release mucoadhesive dosage form of TBN and LGN can be an effective and alternative option to conventional delivery.

Preparation and evaluation of fast-dissolving films of etilefrine hydrochloride for practical buccal dosing.

Etilefrine hydrochloride (ET) is an important drug in the treatment of hypotension, and parenteral injections and oral tablets are the conventional dosage forms. However, parenteral injections may cause abnormally high plasma levels as well as pain and necrosis, and oral tablets undergo first-pass metabolism. Although fast-dissolving buccal tablets were previously reported, the initial absorption rate was a little slow and the plasma levels were varied extensively. Recently, many films have been developed as novel dosage forms. Therefore, in the present study, film dosage forms containing ET were produced using water-soluble polymers and glycerin (GLY) as excipients to obtain a practical buccal dosage form. Films composed of ET, GLY, and sodium alginate (AL) exhibited good physical characteristics and rapid release in vitro (more than 70% at 2 min). The compacted AL film containing 2 mg ET (1 × 1 cm) exhibited rapid absorption (>19 ng/mL at 0.5 h), maintained an effective plasma level (>7 ng/mL) for a long time period (0.5-4 h), and had an adequate plasma concentration-time profile with a smaller standard error (<15.3 ng/mL). These results suggest that the present compacted buccal film is a superior dosage form of ET for practical use.

Formulation of instant disintegrating buccal films without using disintegrant: An in-vitro study.

The current study was conducted to fabricate Metoclopramide HCL (MCH) and Sumatriptan succinate (SS) instant release buccal films (IRBF) without using any super disintegrant. The solvent casting method was used for the preparation of IRBFs and prepared IRBFs were physicochemically evaluated. Spectrophotometric analysis was done to determine the lambda max followed by the linearity determination of both drugs. Different concentrations such as 100, 125, and 150mg of hydrophilic polymer (HPMC E5) were employed but the concentration of glycerol was variable. Comparatively better results were observed for the formulation with 150mg of HPMC E5 and 30% glycerol. Formulated IRBFs showed good tensile strength with a mean disintegration time of 12.4-28.4 seconds and rapid dissolution with more than 50% drug release within 2 minutes. It was concluded that the chosen combination of polymers was appropriate for the fabrication of MCH and SS buccal strips.

Optimization of metronidazole SR buccal tablet for gingivitis using genetic algorithm.

Gingivitis is a condition that needs sustained concentration of antibiotic locally over extended period of time. The current study aimed to formulate and evaluate the sustained and localized release of metronidazole (MTZ) as mucoadhesive buccal tablet containing hydroxypropylmethyl cellulose (HPMC), Carbopol 940® (CP), carboxymethylcellulose (CMC) and ethyl cellulose (EC) as mucoadhesive polymers. Tablets were directly compressed with proportions of polymeric blends (F1-F16). The results indicated that weight variation (249±2.10mg) and friability (0.21%) were within USP compendial limits. Maximum mucoadhesive strength and time were depicted by F1 and F14 which were 28.47g and 12hr respectively. Formulations, except F4, were within physiological pH limit. Maximum swellability index (261.9%) was exhibited by F16, at 8 hr, containing highest concentration of CP, HPMC and additional CMC. For in vitro release, the pre-set 8 hr complete release were shown by formulations, F15 and F16 which were 100% and 97%, respectively. Genetic algorithm was applied on the attributes to optimize polymeric response in accordance with desirability. The software predicted composition (F17) was tested which revealed that physical characteristics were in accordance with the compendial standards. The release kinetics, evaluated through DDsolver⌖, suggested that release of MTZ followed non-Fickian diffusion type in Korsmeyer-Peppas model. Therefore, MTZ, if delivered as mucoadhesive buccal formulation (F17) containing amounts (mg) of CP (16.4), HPMC (78.7), CMC (8.3) and EC (10.5) will simulate satisfactory release i.e. 96% at 8 hr in simulated buccal fluid.

Safety and tolerability associated with chronic intermittent use of diazepam buccal film in adult, adolescent, and pediatric patients with epilepsy.

OBJECTIVE: Diazepam buccal film (DBF) is in development for treatment of patients experiencing bouts of increased seizure activity. We assessed safety, tolerability, and usability of self- or caregiver-administered DBF in the outpatient setting. METHODS: Patients aged 2-65 years needing treatment with a rescue benzodiazepine at least once monthly were eligible for the study. DBF (5-17.5 mg) was dispensed based on age and body weight. Patients/caregivers administered DBF for up to five seizure episodes per month. Adverse events (AEs) and usability assessments were recorded after the first dose, then every 3 months. RESULTS: Onehundred eighteen patients who used ≥1 DBF dose (adults, n = 82; adolescents, n = 19; children, n = 17) were enrolled. Eleven treatment-related AEs (10 being mild or moderate in severity) occurred in nine (7.6%) patients over a mean of 243 days of follow-up. No patient discontinued participation because of AEs. Mild local buccal discomfort, buccal swelling, and cheek skin sensitivity were reported by one patient each. Twenty-two serious AEs were reported; one was treatment-related. The three deaths reported, all unrelated to DBF, resulted from seizures or seizure with brain malignancy. Self-administration by adults was attempted on 23.6% (188/795) of use occasions. Administration of DBF occurred under ictal or peri-ictal conditions on 49.5% (538/1087) of use occasions, and DBF was successfully administered on a first or second attempt on 96.6% (1050/1087) of use occasions. Overall, patients received their dose of DBF on 99.2% (1078/1087) of use occasions. A second DBF dose was required within 24 hours after the first dose on 8.5% (92/1087) of use occasions. SIGNIFICANCE: In this observational study of chronic intermittent use, DBF was easy to administer, safe, and well tolerated in adult, adolescent, and pediatric patients with epilepsy experiencing seizure emergencies. DBF can be readily self-administered by adults with epilepsy, as well as successfully administered by a caregiver in seizure emergencies.

Electrospun α-Lactalbumin Nanofibers for Site-Specific and Fast-Onset Delivery of Nicotine in the Oral Cavity: An In Vitro, Ex Vivo, and Tissue Spatial Distribution Study.

Nicotine replacement therapy (NRT) formulations for oromucosal administration induce a delayed rise in nicotine blood levels as opposed to the immediate nicotine increase obtained from cigarette smoking, this being a shortcoming of the therapy. Here, we demonstrate that α-lactalbumin/polyethylene oxide (ALA/PEO) electrospun nanofibers constitute an efficient oromucosal delivery system for fast-onset nicotine delivery of high relevance for acute dosing NRT applications. In vitro, nicotine-loaded nanofibers showed fast disintegration in water, with a weight loss up to 40% within minutes, and a faster nicotine release (26.1 ± 4.6% after 1 min of incubation) of the loaded nicotine compared to two relevant marketed NRT formulations with a comparable nicotine dose (i.e., 7.9 ± 5.1 and 2.2 ± 0.3% nicotine was released from a lozenge and a sublingual tablet, respectively). Model-fitting of the release data indicated that the release mechanism of nicotine from the hydrophilic nanofibers was possibly governed by more than one type of release phenomena. Remarkably, ex vivo studies using porcine buccal mucosa demonstrated a more efficient permeation of the nicotine released from the nanofibers [flux of 1.06 ± 0.22 nmol/(cm2·min)] compared to when dosing even a ten-fold concentrated nicotine solution [flux of 0.17 ± 0.14 nmol/(cm2·min)]. Moreover, matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MS) imaging of ex vivo porcine buccal mucosa exposed to nicotine-loaded nanofibers clearly revealed higher amounts of nicotine throughout the epithelium, as well as in the lamina propria and submucosa of the tissue. Our findings suggest that nicotine-loaded ALA/PEO nanofibers have potential as a mucosal, fast-releasing, and biocompatible delivery system for nicotine, which can overcome the limitations of the currently marketed NRTs.

Impact of cyclodextrin derivatives on systemic release of duloxetine HCl via buccal route.

Aim: The aim of this work was to develop buccoadhesive tablets for the systemic delivery of duloxetine HCl (DXT) using more soluble derivatives of ß-cyclodextrin, i.e. hydroxypropyl-ß-cyclodextrin (HPßCD) and sulfobutylether-ß-cyclodextrin (SBEßCD) and to investigate enhanced cellular uptake of inclusion complexed drug.Materials and methods: Freeze dried and spray dried complexes of both cyclodextrin derivatives with DXT (1:1 molar) were prepared and characterized with DSC, FTIR, and PXRD techniques. C971 and PC, on the basis of swelling behavior, erosion and in vitro residence time, were selected for further study at different levels (-1, 0, +1) to optimize the formulation in terms of enhanced drug release and ex vivo permeation.Results: SBEßCD based complexes show more aqueous solubility of DXT (0.782 and 0.958 mM) and more complexation efficiency compared to HPßCD at 25 °C and 37 °C, respectively. Apparent stability constant was reported to be higher (1109.94 and 1693.25 M-1) for DXT-SBEßCD at 25 °C and 37 °C, respectively, than the corresponding values for DXT-HPßCD systems. Enhanced cellular uptake using fibroblast cells was revealed for complexed drug compared to free drug .Conclusion: Both cyclodextrin derivatives are able to enhance drug release and permeation in vitro and ex vivo.