Faster Onset Of Action Research Articles

Single-Blind Placebo-Controlled Response Test with Phenytoin 10% Cream in Neuropathic Pain Patients.

Background: Phenytoin cream applied topically has been explored in neuropathic pain conditions. In several case series, phenytoin 5% and 10% cream could reduce pain in a clinically relevant way with a fast onset of action within 30 min, and with positive effects on sleep. Objective: To evaluate a single-blind placebo-controlled response test (SIBRET) for use in clinical practice. Materials and Methods: Patients with localized neuropathic pain, having an equal pain intensity in at least 2 areas (e.g., both feet), and a pain intensity of at least 4 on the 11-point numerical rating scale (NRS), were selected to perform the SIBRET. In one area, placebo cream consisting of the base cream was applied, and on the other area, phenytoin 10% cream was applied with separate hands to avoid contamination. Responders were defined as patients who experienced within 30 min at least 2-points difference as scored on the NRS, between the phenytoin 10% and the placebo cream applied areas, in favor of the former. Responders were subsequently prescribed phenytoin 10% cream. Results: Of the 21 patients, 15 patients (71.45%) were classified as responders. The mean pain reduction after 30 min as measured with the NRS in the phenytoin 10% cream area was 3.3 (SD: 1.3) and in the placebo cream area 1.2 (SD: 1.1). The difference of the mean percentage pain reduction between phenytoin 10% cream and placebo cream was 33.2% (SD: 17.6, p < 0.001). Using a 50% reduction on the NRS as a full response criterion, we could identify 57.1% of responders on phenytoin 10% cream and only 9.5% responders on placebo cream. Conclusions: The SIBRET helps patients and clinicians to quickly identify the appropriate treatment and can thus be seen as an important contributor to the domain of personalized medicine in pain. These results can also be regarded as a proof of principle for the analgesic activity of 10% phenytoin cream.

The behavior of Italian allergists in prescribing allergen immunotherapy for house dust mites allergy.

The meeting 'Clinical Evidence, Extracts Quality and Biotechnology Innovation in Allergen Immunotherapy' held in Trieste (Italy) on 1 October 2017 concerned the outcomes of a real-world survey conducted on a group of Italian allergists about allergen immunotherapy (AIT) for house dust mites allergy. It pointed out: allergist's confidence that AIT should be prescribed continuously; tablets seem to be well accepted by patients and effective in most subjects with a fast onset of action (3-6 months); combined score for symptom severity and medication use is universally assessed; there is disagreement about the diagnosis of house dust mites allergy, the quote of AIT prescription, the choice for AIT route of administration, assessment of serum IgE and perception of patient's adherence.

Design, synthesis and biological evaluation of 5-(2-amino-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one derivatives as potent β2-adrenoceptor agonists.

A series of novel β2-adrenoceptor agonists with a 5-(2-amino-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one moiety was designed, synthesized and evaluated for biological activity in human embryonic kidney 293 cells and isolated guinea pig trachea. Compounds 9g and (R)-18c exhibited the most excellent β2-adrenoceptor agonistic effects and high β2/β1-selectivity with EC50 values of 36 pM for 9g and 21 pM for (R)-18c. They produced potent airway smooth muscle relaxant effects with fast onset of action and long duration of action in an in vitro guinea pig trachea model of bronchodilation. These results support further development of the two compounds into drug candidates.

An improved water-soluble prodrug of propofol with high molecular utilization and rapid onset of action

Water-soluble prodrugs of propofol often carry an excess of propofol at the effective dose and have a slower onset of action. Sustained release of the original drug can result in propofol accumulation in the body after administration, causing delays in wakefulness. This situation causes the prodrug to lose the benefits of rapid onset and recovery from the effects of propofol. In the present study, HX0921 (sodium 2-(2-(2,6-diisopropylphenoxy)-2-oxoethoxy)acetate), an improved prodrug of propofol with high utilization of propofol and fast onset of action, was studied. The rate of propofol release from HX0921 was much faster than that from fospropofol (a marketed propofol prodrug) in rat plasma. The 50% effective dose (ED50) of propofol, HX0921 and fospropofol to induce anesthesia in rats was 5.78, 22.19 and 42.44 mg/kg, respectively. After administration at 2 × ED50, the onset time of anesthesia in the HX0921 group was significantly shorter than that in the fospropofol group (0.26 ± 0.15 min vs. 2.24 ± 0.35 min, P < 0.01) and the duration of anesthesia in the HX0921 group was also significantly shorter than that in the fospropofol group (22.35 ± 4.05 min vs. 29.15 ± 5.25 min, P < 0.01). These results suggest that the rapid onset and short action time of HX0921 was due to the rapid release and high molecular utilization of propofol carried by HX0921.

Impact of Ocular Compatible Lipoids and Castor Oil in Fabrication of Brimonidine Tartrate Nanoemulsions by 33 Full Factorial Design.

Brimonidine Tartrate (BRT) is used in the treatment of glaucoma. Brimonidine tartrate nanoemulsion was fabricated in this research work to enhance the permeability through barriers and faster onset of action and therapeutic effect. To fabricate an ocular compatible nanoemulsion of brimonidine tartrate by using surfactant and co-surfactants. The experimental work involved compatibility studies by using FTIR, DSC and crystallinity study by XRD. The prepared nanoemulsion was studied by photon correlation spectroscopy by Malvern S90 for the particle size analysis and characterized for Z average value (d.nm.) and PDI. Further studies were conducted by laser light scattering technique by delsanano common and TEM. The study demonstrated that the formulations BN2, BN3, BN10 demonstrated the z average value of 19.48, 22.14,26.50 d.nm. With 0.337, 0.270, 0.289 PDI respectively, the formulae BN2, BN3, BN10 demonstrated the distribution average diameter (nm) of 376.8 + 258.4, 542.8 + 494.4, 398.8 + 263.9 with the diameter of 267.5, 298.5, 272.7, respectively. The zeta potential of BN10 was -21.26 mV and other parameters such as TEM and drug release studies were also reported. The nanoemulsion of brimonidine tartrate was prepared successfully by using castor oil, Lipoid S75 (Fat free soybean phospholipids with 70% phosphatidylcholine), Lipoid E80 (Egg phospholipids with 80% phosphatidylcholine) and PF- 68. The optimised formula demonstrated the lower droplet size, satisfactory zeta potential, and high drug loading and reproducible drug release profile. Brimonididne taratarate is reported in various recent patents for various applications and is the potential candidate for future therapy. Nanoemulsion is widely explored as potential alternatives for conventional ophthalmic formulation based approaches. It enhances the ocular bioavailability by reducing the drug protein binding, increasing the corneal resident time, enhancing the drug permeability and providing a sustained drug release.It reported a significant increase in therapeutic efficacy for various chronic ocular disease states of both the anterior and posterior ocular segments.

Capsaicin 8% Dermal Patch: A Review in Peripheral Neuropathic Pain.

The adhesive capsaicin dermal patch (Qutenza®) delivers a high concentration (8% w/w) of synthetic capsaicin, a highly selective agonist of transient receptor potential vanilloid-1 (TRPV-1), directly to the site of pain. The capsaicin 8% dermal patch is indicated in the EU for the treatment of peripheral neuropathic pain (PNP) in adults, either alone or in combination with other medicinal products for pain. In patients with painful diabetic peripheral neuropathy, a single 30-min application of the capsaicin 8% dermal patch provided 12weeks of pain relief and improved sleep quality compared with placebo. Repeat treatment with the capsaicin 8% dermal patch plus standard of care over 52weeks provided sustained pain relief, with no negative neurological effects compared with standard of care alone. The capsaicin 8% dermal patch was non-inferior to oral pregabalin in relieving pain in patients with non-diabetic PNP, with a faster onset of action and greater treatment satisfaction. A single 60-min application of the capsaicin 8% dermal patch provided rapid and sustained pain relief in patients with postherpetic neuralgia. Results in patients with HIV-associated neuropathy were equivocal, with a significant improvement in pain intensity observed in one trial, but not in the other. The capsaicin 8% dermal patch was generally well tolerated; transient application-site reactions were the most common adverse events. In conclusion, the capsaicin 8% dermal patch is a useful addition to the treatment options currently available for patients with PNP.

Orally inhaled migraine therapy: Where are we now?

Migraine is a debilitating disease that affects 9% of men and 19% of women worldwide with high socio-economic and personal impact. Surveys indicate that migraineurs are among the most dissatisfied with available therapeutic options, predominantly given via oral or injectable routes, citing side effects as the primary complaint. Orally inhaled therapies have the potential to offer faster onset of action with fewer side effects compared to existing therapies, yet development has stalled. Despite emerging therapies such as calcitonin gene-related peptide antagonists, there are still good opportunities for repositioning migraine drugs via the inhaled route.

Pharmacokinetic and Pharmacodynamic Properties of a Novel "Superfast" Insulin Aspart Formulation

Background: An insulin with a significantly faster onset of action compared to current state-of-the-art products will improve postprandial glycaemic control, reduce variability, improve HbA1c and increase flexibility. A superfast insulin is a key component for the development of efficient closed-loop pump systems. Method: A superfast formulation, utilising excipients with metal ion binding constants critical in controlling injection site absorption, was investigated in diabetic mini swine in a randomized, cross-over experiment. Ten male animals received 0.2 U/kg insulin via subcutaneous injection. At standardized intervals post-injection, blood glucose and insulin were measured. Results: Pharmacodynamic (PD) and pharmacokinetic (PK) properties of Superfast insulin were compared to an ultra-rapid control composition including nicotinamide. Tmax (22.5 minutes vs. 41.9 minutes) and T1/2max (7.9 minutes vs. 11.9 minutes) were significantly (P&amp;lt;0.01 and P&amp;lt;0.02) shorter for Superfast insulin, with a correspondingly faster glucose lowering action (Figure 1). Figure 1a) PD and 1b) PK profile of 100U/mL Superfast insulin (red) in comparison to an ultra-rapid acting insulin control containing nicotinamide (blue)1a. Conclusion: This novel formulation represents a unique superfast prandial insulin that more closely matches a physiological response to blood glucose with the potential to be a major advancement for diabetes care. Disclosure T.R. Pieber: Consultant; Self; Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Employee; Self; CBmed. Research Support; Self; Novo Nordisk A/S, AstraZeneca. S.J. Howell: None. J. Jezek: None. D.J. Gerring: Employee; Self; Arecor Limited.

Sublingual Versus Oral Captopril for Decreasing Blood Pressure in Hypertension Urgency: A Randomized Clinical Trial

Background: Captopril, a short-acting antihypertensive agent, is widely used in case of emergency to control blood pressure. Although sublingual Captopril has a faster onset of action, it is less tolerated. Objectives: This study aimed to evaluate the efficacy, side effects, and tolerability of sublingual versus oral captopril in an emergency setting. Methods: Hypertensive patients, without acute target organ damage were randomly administered 25 mg Captopril sublingually or orally (35 patients in each group) using block randomization. Blood pressure was measured at 0, 10, 20, 30, 45, 60, and 120 minutes after the administration. Patient satisfaction was subjectively scored on a scale of 1 - 10, and any side effect was recorded (Iranian registered clinical trials # IRCT2015110924963N1). Results: The mean age of the study groups was 59.61 ± 9.34 years. Systolic and mean blood pressure significantly decreased after 10, 20, and 30 minutes of sublingual administration (P < 0.05), but diastolic blood pressure did not decrease. This difference in the blood pressure reducing effect decreased by 60 and 90 minutes and almost equalized after 90 minutes. Headache was observed as a side effect in two patients in the sublingual group. The convenience and satisfaction scores were much lower in the sublingual group (median of 6 (25th percentile: 6, 75th percentile: 7) in sublingual group versus median of 10 (9, 10) in Captopril group, P < 0.001). Conclusions: In our study, the systolic and mean blood pressure decreased more rapidly in the sublingual Captopril group than in the oral Captopril group in the first 30 minutes after administration. Patients better tolerated the oral preparation, and the difference in the blood pressure reducing effect between the groups almost equalized after 90 minutes.

AN OVERVIEW ABOUT NOVEL FAST DISSOLVING ORAL FILMS

Nowadays, novel fast dissolving oral films (FDF) have come in existence as an alternative dosage form in comparison with tablet, capsules, syrup and other oral dosage forms with respect to patient convenience and compliance. Fast dissolving oral films are helpful to paediatric and geriatric patients who experience difficulties in swallowing traditional oral solid-dosage forms. The FDF drug delivery systems are solid dosage form which disintegrate or dissolve within seconds when placed in the mouth cavity without need of water or chewing. FDF provide better drug dissolution, faster onset of action, bypassing the first pass metabolism of drugs and thus enhance their oral bioavailability with reduced dosing frequency. These formulations are suitable for cough, cold, sore throat, allergenic conditions, nausea, pain, hypertension and CNS disorders. The present review provides the details about the recent advancement in design and development of oral fast dissolving film.

AN OVERVIEW ABOUT NOVEL FAST DISSOLVING ORAL FILMS

Nowadays, novel fast dissolving oral films (FDF) have come in existence as an alternative dosage form in comparison with tablet, capsules, syrup and other oral dosage forms with respect to patient convenience and compliance. Fast dissolving oral films are helpful to paediatric and geriatric patients who experience difficulties in swallowing traditional oral solid-dosage forms. The FDF drug delivery systems are solid dosage form which disintegrate or dissolve within seconds when placed in the mouth cavity without need of water or chewing. FDF provide better drug dissolution, faster onset of action, bypassing the first pass metabolism of drugs and thus enhance their oral bioavailability with reduced dosing frequency. These formulations are suitable for cough, cold, sore throat, allergenic conditions, nausea, pain, hypertension and CNS disorders. The present review provides the details about the recent advancement in design and development of oral fast dissolving film.

Safety of bolus-dose phenylephrine for hypotensive emergency department patients

IntroductionBolus-dose phenylephrine (BDPE) is routinely used to treat hypotension in the operating room. BDPE's fast onset of action and ability to be administered peripherally have prompted calls for its use in the Emergency Department (ED). There are few published data on the safety of BDPE use in the ED. Primary concerns include BDPE's potential to cause dangerous hypertension or reflex bradycardia. We hypothesize that BDPE is a safe short-term vasopressor choice for hypotensive ED patients. MethodsWe conducted a structured chart review for all patients who received BDPE from preloaded syringes over 42months. We defined an adverse event (AE) as sBP>180, dBP>110, or HR<50 within 30min of receiving BDPE. We defined a serious adverse event (SAE) as an AE with pharmacologic intervention to correct vital sign abnormality. We also compared mean arterial pressure (MAP), sBP, and dBP pre/post BDPE administration to assess effectiveness. We used a two-sample t-test to assess for differences between the mean delta MAP after low versus high-dose BDPE. ResultsWe identified 181 cases of ED use. 147 cases had complete pre/post vital signs. We identified 5 AEs and no SAEs. Three patients developed sBP>180mmHg. The patients suffered no apparent harm. No patients had dBP>110. Two patients developed bradycardia post-drug. In both cases, MAP improved despite bradycardia. ConclusionsBDPE does not appear to cause reflex bradycardia or hypertension requiring intervention among hypotensive ED patients. The apparent safety of BDPE should be confirmed in prospective trials.

Geriatric-Oriented High Dose Nutraceutical ODTs: Formulation and Physicomechanical Characterization.

Oral disintegrating tablets (ODTs) represent a better option than conventional tablets for geriatric population, owing to their fast onset of action and their better patient compliance. Two principal therapeutic high-dose nutraceuticals; chondroitin sulphate and glucosamine were formulated into an oral disintegration tablet (ODT) intended for sublingual administration, and optimized to improve compliance and achieve rapid onset of action in osteoarthritis treatment. Different formulations were prepared either by melt granulation or direct compression techniques. Excipients at different ratios such as superdisintegrants, pharmaburst™ C1, spray-dried mannitol, and polyethylene glycols were used to enhance the disintegration time for the ODT systems. Although the ODT systems weighed around 1.3 gm with 60% drug load, some systems disintegrated within 2-3 min with 100% drug release. Pharmaburst™ C1 turned out to be the key excipient responsible for the superdisintegration properties of the ODTs. Dissolution enhancement of the two nutraceuticals could be achieved compared to the marketed conventional tablets. The improved disintegration and dissolution properties of our prepared ODTs are expected to enhance the bioavailability of the high dose glucosamine and chondroitin sulphate in comparison with conventional tablets, which delineates them as a promising dosage form for the aforementioned nutraceuticals.

Onset of action for loratadine tablets for the symptomatic control of seasonal allergic rhinitis in adults challenged with ragweed pollen in the Environmental Exposure Unit: a post hoc analysis of total symptom score

BackgroundLoratadine is a second-generation, non-sedating antihistamine used for the relief of allergic rhinitis symptoms. Previous studies reported that when loratadine was encapsulated, the onset of action for symptom relief was 180 min. However, unmodified loratadine tablets were not evaluated at that time. Using data from a previously published Environmental Exposure Unit (EEU) study comparing azelastine nasal spray with loratadine tablets, cetirizine tablets, and placebo, this post hoc analysis determines the onset of action of loratadine tablets (i.e. unmodified) by analyzing the total symptom score for the relief of nasal and ocular seasonal allergic rhinitis (SAR) symptoms.MethodsA Phase IV, randomized, single-center, double-blind, placebo-controlled, double-dummy, four-way crossover study was conducted in the EEU. Seventy participants were randomized sequentially into one of the four treatments during ragweed pollen exposure. Nasal and ocular symptom scores were self-reported by the participants and recorded. The original study analysis was carried out by evaluating the nasal symptom scores only. For this post hoc analysis, both nasal and ocular data from the loratadine and placebo treatment arms were analyzed. The primary endpoint for this analysis was the onset of action of loratadine as measured by the change in total symptom score (TSS) from baseline in comparison to placebo. The onset of ocular symptom relief using the total ocular symptom score (TOSS) was also reported.ResultsLoratadine tablets demonstrated a significant and durable improvement in both TSS (P = .005) and TOSS (P = .013) at 75 min post-treatment administration compared to placebo. The mean proportion of participants reporting none or mild for all component symptoms of TSS and TOSS at 75 min and thereafter was significantly higher in the loratadine (TSS, P = .0005; TOSS, P ≤ .0001) vs. placebo treatment arm.ConclusionsThe onset of action of loratadine tablets was 75 min for the relief of nasal and ocular symptoms in adults with SAR. These results suggest a faster onset of action for loratadine tablets (75 min) compared to previously reported studies which were conducted with modified (i.e. gelatin-encapsulated) loratadine tablets (180 min).Trial registration Clinicaltrials.gov identifier NCT00561717

Other Antidepressants.

Other Antidepressants.

Endoscopy and sedation: an inseparable binomial for the gastroenterologist.

The development of endoscopy and its increasing demand among the population have led to a growing need for propofol-based sedation techniques. Benefit is indisputable for both patients and endoscopists, but some aspects require considering the "who" and "how" of sedation as related to safety and health care costs. Propofol is first-choice in endoscopy for the European Society of Gastrointestinal Endoscopy because of its fast onset of action and short half-life, and many reports exist on its safety when used by gastroenterologists rather than anesthesiologists. In this issue of REED several originals support the efficiency and safety of propofol even for complex, high-risk, or protracted procedures such as endoscopic retrograde cholangiopancreatography (ERCP) and enteroscopy. Propofol may be safely and effectively administered by a team with specific skills acquired through education and using a specific procedure. However, difficulties arise in real-world clinical practice that preclude such training, which in Spain should be included in the MIR (médico interno residente) specialization program curriculum. The Comisión Nacional de Digestivo (Spanish National Commission on Digestive Diseases), sensitive to this training gap, has included in their latest version of the MIR program (under assessment) four additional competences, with number 145 (training in deep sedation) being most relevant here. In addition, the Spanish Society of Gastrointestinal Endoscopy (SEED) has invested significant efforts in sedation training, with over 50 courses on sedation for endoscopists and nurses. Continuing education and training in this field (for instance, refresher courses on advanced cardiopulmonary resuscitation) should be a goal for all endoscopy units. Because of the diversity found among hospitals, with single or multiple endoscopy rooms, efforts should be made to persuade those in charge of gastroenterology and anesthesiology departments to establish the necessary care circuits in order to guarantee patient safety by developing accurate protocols and promoting consensus among the scientific societies involved (Spanish Society for Digestive Diseases [SEPD], SEED and Spanish Society of Anaesthesiology, Resuscitation and Pain Management [SEDAR]) and their respective national commissions.

Development of lamotrigine solid dispersion for the formulation and evaluation of fast dissolving tablets

Lamotrigine is an anticonvulsant drug used in the treatment of epilepsy and bipolar disorders. Its acts primarily by obstructing voltage dependent sodium channel hence a decreased level of excitatory neurotransmitter. Solid dispersion is a newer technique of enhancing the solubility of poorly soluble drugs using suitable polymer. Moreover, for obtaining better drug absorption, faster onset of action and safety regarding its administration fast dissolving tablets are becoming standards. These upon administration into mouth gets rapidly dissolve due to presence of saliva without any need of water. Lamotrigine solid dispersion was prepared using PEG 6000 as polymer in the ratio (1: 1). Fast dissolving tablet of lamotrigine was formulated using 3 different superdisintegrants (crosscarmellose, kollidon, sodium starch glycolate (SSG)) in different ratios. The formulated tablets were then evaluated for its different parameters. The result of invitro dissolution study showed that formulation F5 is most successful as it dissolved in a very short period containing combination of kollidon and SSG in the ratio (1: 3). An increased disintegration time was noted with combination of crosscarmellose and SSG (1: 1) ratio.

Comparison of ultrasound-guided serratus plane block and thoracic paravertebral block for postoperative analgesia after thoracotomy: a randomized controlled trial

Background Post-thoracotomy pain can be severe and difficult to control. Paravertebral block (PVB) has been proven to be effective in controlling post-thoracotomy pain; however, it has its own set of complications. Ultrasound-guided serratus plane block (SPB) is a newly described field block that may provide thoracic wall analgesia. Objective This prospective randomized controlled study was carried out to compare the analgesic effects of PVB and SPB on post-thoracotomy pain. Patients and methods The study was done on 60 adult patients aged 18–65 years undergoing thoracotomy for pulmonary resection. The patients were randomly allocated to receive either thoracic PVB or SPB guided by ultrasound before induction of general anesthesia. The primary outcome was the visual analogue scale, which was recorded on arrival to the ICU and then at 1, 2, 4, 8, 12, 18, and 24 h postoperatively both at rest and during coughing. The secondary outcomes were time to perform the block, onset of sensory block, number of blocked dermatomes, block success rate, total postoperative morphine consumption, and any complications related to the regional block. Results The time to perform the block was significantly shorter in SPB than in PVB (3.76±1.1 vs. 6.14±1.6 min, P Conclusion SPB had a shorter time to perform and a faster onset of action than thoracic PVB and provided adequate analgesia in the early postoperative period; however, postoperative morphine consumption was higher in patients who received SPB.

Comparative evaluation of anesthetic efficacy of warm, buffered and conventional 2% lignocaine for the success of inferior alveolar nerve block (IANB) in mandibular primary molars: A randomized controlled clinical trial.

Background: Maintaining primary teeth in the oral cavity is of prime importance, and grossly carious teeth may require pulp therapy for the same. Pain on injection and incomplete anesthesia causes failure of the procedure and result in fear and anxiety. Various methods have evolved to overcome this; such as distraction, topical anesthesia, etc. A few techniques regaining popularity in dentistry in recent times is the warming or buffering of the solution prior to administration. This study thus aimed to compare and evaluate the anesthetic efficacy and the patient’s pain reaction to pre-warmed, buffered and conventional 2% lignocaine for the success of Inferior Alveolar Nerve Block in mandibular primary molars undergoing pulp therapy. Methods: The study is a randomized, split-mouth trial. Sixty children between six -12 years, requiring pulp therapy bilaterally on mandibular primary molars, were administered conventional, buffered or pre-warmed 2% lignocaine on two separate appointments. Various parameters were assessed using objective and subjective scales. Results: Pre-warmed and buffered anesthetics had lesser pain on injection (p<0.001, p<0.001) and pulp therapy (p=0.001, p=0.014), faster onset of action (p=0.004, p=0.001), lower SEM Sound (p=0.035, p=0.028), Eye (p< 0.001, p=0.013) and Motor (p=0.008, p=0.021) scores and shorter duration of action (p< 0.001, p=0.015). No significant difference was found between the two modified solutions. Thus pre-warmed and buffered anesthetic solutions fared better than the conventional solution for all parameters but had no advantage over each other. Conclusion: Buffering or pre-warming the anesthetic solution reduces pain on administration and during procedures in children. Trial registration number: CTRI/2017/02/007922

FORMULATION AND EVALUATION OF MOUTH DISSOLVING FILM OF TADALAFIL

This research work was aimed to enhance the oral bioavailability and provide faster onset of action of Tadalafil (used for the treatment of the erectile dysfunction (ED) and pulmonary arterial hypertension) by formulating its mouth dissolving film (MDF). Tadalafil belongs to BCS class II and the oral bioavailability of it’s about 28%. The MDF of Tadalafil was prepared by solvent casting method using HPMC-E5 (film forming agent), Methyl cellulose (thickening agent), Propylene glycol (plasticizer), Tween-80 (solubilizing agent), Microcrystalline cellulose (disintegrating agent), Citric acid (saliva stimulating agent), Sucrose (sweetening agent), Vanillin (flavoring agent), EDTA disodium (preservative). The formulation was optimized by two factors, three level (23) full factorial design using concentration of Plasticizer (X1) and concentration of film forming agent (X2) as independent variables and formulation was evaluated for uniformity of mass, thickness, folding endurance, drug content uniformity, in-vitro disintegration, in-vitro drug dissolution study and stability study. Based on results it was concluded that MDF (F5) showed enhanced bioavailability and faster onset of action as compared to available tablet dosage form.