Local Anesthetic Activity Research Articles

Development of the formulation of “Artproment®” combined gel for application in sports medicine

Based on the data of pharmaco-technological and physico-chemical studies conducted the formulation of the gel with the anti-inflammatory and local anesthetic action under the conditional name “Arthroment ®” has been theoretically and experimentally substantiated in the pharmacy and industrial conditions. It is intended for application in a complex treatment of mechanical injuries and post-traumatic inflammations of extremities soft tissues, diseases of the locomotor apparatus (tendons, muscles and joints), musculoskeletal injuries that are characteristic for sports medicine and sports during the rehabilitation period such as bruises, dislocations, sprains, ruptures of ligaments, tendons, etc. The objects of research were model samples of “Artproment®” gel, which includes such active pharmaceutical ingredients (APhI) in its composition as propolis phenolic hydrophobic drug, articaine hydrochloride, menthol (levomenthol) and rosemary oil, as well as the following excipients: a gelation agent (Ultrez-10 NF carbomer), a neutralizer (trometamol), a preservative, nonaqueous solvent (propylene glycol), ethanol and purified water. The results of the experimental research were used when developing the technological process flowchart for preparing “Artproment®” gel in the conditions of pharmacy production and standard operating procedure on the drug studied. Taking into account the physicochemical properties and according to the research results on solubility of APhI in the composition of the drug the technological process flowchart for manufacturing the combined gel industrially and the project of manufacturing instructions have been developed; technological parameters of its manufacturing have been substantiated; the optimal amount of solvents required for performing each technological stage has been calculated taking into account the solubility of the gel components, consequence and phasing of their mixing, temperature and other parameters affecting the quality and stability of the drug; and the formulation of “Artproment®” combined gel has been tested in the pharmacy and industrial conditions.

The experimental study of the specific pharmacological action of «Artproment» combined gel

The preclinical experimental research concerning the study of the specific pharmacological action of "ArtpromentÒ" gel has been done. The gel developed contains propolis phenolic hydrophobic drug, articaine hydrochloride, menthol and rosemary oil in its composition. The medicine is planned to application in sports medicine with the purpose of treating traumatic injuries of organs of the locomotor apparatus accompanied with sport traumas (bruises, dislocations, sprains, ruptures of ligaments, tendons, etc.).In this work the pharmacological, physiological, instrumental methods of research and methods of mathematical statistics have been used.The study of the analgesic and local anesthetic action of the gel developed was conducted at the premises of the Central Research Laboratory of NUPh under the supervision of Doctor of Pharmacy, professor L.V.Iakovlieva on the model of tail thermoirritation in white rats weighing 180.0-200.0 g. The analgesic and local anesthetic actions were estimated by the ability of the medicine studied to change the pain threshold (duration of the latent period, sеc.) in animals of the test group comparing to the control group in the dose of 25 mg/cm2 and the base in the dose of 30 mg/cm2 after application to the tail.The results of the experiment testify that when studying the influence of the combined gel on the course of the experimental nociceptive response of the central origin the significant analgesic action of "ArtpromentÒ" medicine has been determined; its highest intensity was observed in 2.5 and 3.5 hours after application and is 52 % and 59 %, respectively. Despite the fact that the progress of the pain syndrome in the model of tail thermoirritation is mediated by the central nervous system, it is possible to conclude that the developed gel has an expressed analgesic and local anesthetic action. The medicine shows the significant anti-edema action at the level of the reference medicine "Diclofen-gel" on the carrageenan-induced paw oedema model.Taking into account that injuries of organs of the locomotor apparatus cause manifestation of inflammation and development of oedema it is expedient to study the anti-edema action of "ArtpromentÒ" gel in comparison with "Diclofen-gel", which is the complete analogue by the specific pharmacological action and the partial analogue by the composition. The research was conducted using the carrageenan-induced paw edema model in 24 rats weighing 180.0-200.0 g. Edema was caused by subplantar introduction of 0.1 ml of 1 % solution of carrageenin into one of the hind limbs of the animals of the test and control groups. Development of oedema was registered by increase of the paw’s volume measured in dynamics in 1; 2; 3; 4 і 5 hours with the help of a mechanical oncometer according to A.S. Zakharevsky.The experimental results indicated that the medicine under research exhibits a significant anti-edema action on the level of the reference medicine "Diclofen-gel". It has been experimentally found that the average anti-edema action of the "ArtpromentÒ" gel within 5 hours is 39 %, "Diclofen-gel" – 48 %; it is the evidence of their similarity in the absence of confidence in the index divergence. Therefore, the developed medicine shows the expressed anti-edema action at the level of 40-50 %, this property together with the analgesic and local anesthetic activities allows to recommend it for further study with the purpose of creation of the local medicine for traumatic injuries of the locomotor system treating accompanied with sports traumas (bruises, dislocations, sprains, ruptures of ligaments, tendons, etc.).

Improvement of Lidocaine Local Anesthetic Action Using Lallemantia royleana Seed Mucilage as an Excipient.

Lallemantia royleana (Balangu) is a well known Iranian medicinal plant that its seed mucilage has many applications in modern pharmacology. Plant mucilage traditionally was used as a gel supplement, and natural matrix for sustained release of drugs. But it seems that these compounds are not a simple additive and also have many undiscovered pharmacological properties. In this research, the anesthetic action of gel prepared from Balangu mucilage alone and its mixture with lidocaine hydrochloride are compared with the effect of commercial 2% lidocaine gel by rat tail flick test. Mucilage of Balangu seed alone showed analgesic effect. Duration and potency of anesthesia induced by gel containing mucilage alone (0.01 g/mL) were identical to commercial 2% lidocaine gel. But, local anesthetic potency and duration of gel made from 2% lidocaine-mucilage gel mixture was significantly higher than commercial 2% lidocaine gel. The gel prepared from mucilage causes a good analgesia with unknown mechanism. Besides, mixture of Balangu mucilage prepared gel with lidocaine improves lidocaine anesthesia. The increase in potency of lidocaine action results from mucilage dermal penetration enhancing effects; and longer anesthetic duration of this mixture are related to the capability of mucilage based gel for sustained drug release.

A systematic review and meta-analysis of perineural dexamethasone for peripheral nerve blocks.

We systematically reviewed the safety and efficacy of perineural dexamethasone as an adjunct for peripheral nerve blockade in 29 controlled trials of 1695 participants. We grouped trials by the duration of local anaesthetic action (short- or medium- vs long-term). Dexamethasone increased the mean (95% CI) duration of analgesia by 233 (172-295) min when injected with short- or medium-term action local anaesthetics and by 488 (419-557) min when injected with long-term action local anaesthetics, p < 0.00001 for both. However, these results should be interpreted with caution due to the extreme heterogeneity of results, with I2 exceeding 90% for both analyses. Meta-regression did not show an interaction between dose of perineural dexamethasone (4-10 mg) and duration of analgesia (r2 = 0.02, p = 0.54). There were no differences between 4 and 8 mg dexamethasone on subgroup analysis.

The study of comparative analgesic activity of Lidocaine and Ropivacaine on albino rats

Analgesics are the drugs which possess significant pain relieving properties by acting on the CNS or peripheral pain receptors without significantly affecting consciousness. Lidocaine and Ropivacaine are well studied individually; but there are conflicting reports of the comparison of actions between these two drugs both in experimental and clinical trials. Total of 30 rats were taken, they were divided into six groups each containing 5 rats. The analgesic activity of drugs was studied by measuring drug-induced changes in the sensitivity of the pre-screened mice to heat stress applied to their tails (reaction time: 2-4 sec). With increasing the dose of the analgesics from 6.25 to 25µg/kg the analgesic action occurred earlier. A clinical significance is that Lidocaine has its some better analgesic effect than Ropivacaine. As known, the dose of Lidocaine for local anesthetic action is < 7mgs/kg body weight, and of Ropivacaine it is <8mgs/kg body weight. But in our study a dose of the analgesics was low, up to 25µg/kg only. Because of this low dose, the mechanism of analgesic action of the drugs is different, and it is discussed in this paper.

Aconitum and Delphinium Diterpenoid Alkaloids of Local Anesthetic Activity: Comparative QSAR Analysis Based on GA-MLRA/PLS and Optimal Descriptors Approach

The duration of anesthesia (related to protein binding of a drug) and the onset time (determined by the pKa) are important characteristics in assessment of local anesthetic agents. They are known to be affected by a number of factors. Early studies of antiarrhythmic diterpenoid alkaloids from plants Aconitum and Delphinium suggested that they possess local anesthetic activity due to their ability to suppress sodium currents of excited membranes.In this study we utilized toxicity, duration, and onset of action as endpoints to construct Quantitative Structure–Activity Relationship (QSAR) models for the series of 34 diterpenoid alkaloids characterized by local anesthetic activity using genetic algorithm-based multiple linear regression analysis/partial least squares and simplified molecular input line entry system (SMILES)-based optimal descriptors approach. The developed QSAR models correctly reflected factors that determine three endpoints of interest. Toxicity correlates with descriptors describing partition and reactivity of compounds. The duration of anesthesia was encoded by the parameters defining the ability of a compound to bind at the receptor site. The size and number of H-bond acceptor atoms were found not to favor the speed of onset, while topographic electronic descriptor demonstrated strong positive effect on it. SMILES-based optimal descriptors approach resulted in overall improvement of models. This approach was shown to be more sensitive to structural peculiarities of molecules than regression methods.The results clearly indicate that obtained QSARs are able to provide distinct rationales for compounds optimization with respect to particular endpoint.

Preparation of an Inclusion Complex of 1-(3-n-butoxypropyl)-4-vinylacetylen-4-benzoyloxypiperidine with B-cyclodextrin and its Local Anesthetic Activity

Complex formation of 1-(3-n-butoxypropyl)-4-vinylacetylene-4-benzoyloxypiperidine with β-cyclodextrin was studied by NMR spectroscopy. The structural characteristics and composition (1:2) of the resulting inclusion complex of 1-(3-n-butoxypropyl)-4-vinylacetylene-4-benzoyloxypiperidine with β-cyclodextrin in aqueous solution were identified. The local anesthetic activity of the resulting preparation was assessed; the complex was found to have greater anesthetic activity greater than reference agents.

Beta-caryophyllene modulates expression of stress response genes and mediates longevity in Caenorhabditis elegans

Beta-caryophyllene (BCP) is a natural bicyclic sesquiterpene and is a FDA approved food additive, found as an active ingredient in essential oils of numerous edible plants. It possesses a wide range of biological activities including anti-oxidant, anti-inflammatory, anti-cancerous and local anesthetic actions. We used the well established Caenorhabditis elegans model system to elucidate the stress modulatory and lifespan prolonging action of BCP. The present study for the first time reports the lifespan extension and stress modulation potential of BCP in C. elegans. Upon evaluation, it was found that 50μM dose of BCP increased the lifespan of C. elegans by over 22% (P≤0.0001) and significantly reduced intracellular free radical levels, maintaining cellular redox homeostasis. Moreover, the results suggest that BCP modulates feeding behavior, pharyngeal pumping and body size effectively. Further, this compound also exhibited significant reduction in intestinal lipofuscin levels. In the present investigation, we have predicted possible biological molecular targets for BCP using molecular docking approaches and BCP was found to have interaction with SIR-2.1, SKN-1 and DAF-16. The prediction was further validated in vivo using mutants and transgenic strains unraveling underlying genetic mechanism. It was observed that BCP increased lifespan of mev-1 and daf-16 but failed to augment lifespan in eat-2, sir-2.1 and skn-1 mutants. Relative quantification of mRNA demonstrated that several genes regulating oxidative stress, xenobiotic detoxification and longevity were modulated by BCP treatment. The study unravels the involvement of multiple signaling pathways in BCP mediated lifespan extension.

Synthesis and Local-Anesthetic Activity of New Arylpyruvic Acid Derivatives

N-{2[((1Z)-1-{[(2, 6-dimethylphenyl)amino]carbonyl}-3-oxo-3-arylprop-1-en-1-yl)amino]ethyl}-N,N-dimethyl- 1-oxoethanaminium chlorides were synthesized by acylation of arylpyruvic acid enaminoamides. Compounds with high local-anesthetic activity were found among them.

Получение комплекса включения 1-(3-н-бутоксипропил)- 4-винилацетилен-4-бензоилоксипиперидина с &amp;beta;-циклодекстрином и его местноанестезирующая активность

Изучено комплексообразование 1-(3-н-бутоксипропил)-4-винилацетилен-4-бензоилоксипиперидина с b-циклодекстрином методами спектроскопии ЯМР. Установлены структурные особенности и состав (1:2) полученного комплекса включения 1-(3-н-бутоксипропил)-4-винилацетилен-4-бензолоиксипиперидина с b-циклодекстрином в водном растворе. Исследована местноанестезирующая активность полученного препарата; выявлено, что данный комплекс обладает анестезирующей активностью, превышающей активность препаратов сравнения.

Efficacy of Ambroxol lozenges for pharyngitis: a meta-analysis

BackgroundAmbroxol has a local anaesthetic action and is marketed for pain relief for sore throat. The objective is to examine the efficacy and safety of ambroxol for the relief of pain associated with acute uncomplicated sore throat.MethodsA systematic review of the literature and meta-analysis. Selection criteria consisted of randomized controlled trials which compared ambroxol to placebo or any other treatment for sore throat. Two reviewers independently assessed for relevance, inclusion, and risk of bias. Weighted mean differences (WMDs) were calculated and are reported with corresponding 95% confidence intervals (CIs).Results and conclusionFrom 14 potentially relevant citations, five trials reported in three publications met the inclusion criteria, three of them were published twice. Ambroxol lozenges were compared in different dosages (5–30 mg) with mint flavoured lozenges and once with benzocaine. Main outcome was a ratio of pain reduction measured repeatedly over 3 h compared to baseline on 6-item verbal rating scale. A total of 1.772 adult patients participated in the trials. Pain intensity decreased in both study arms. A meta-analysis of the 5 controlled trials resulted in a difference in pain reduction compared to placebo of -0.11 (95% CI [-0.15, -0.07]; p < 0.0001) favouring ambroxol 20 mg. Quality of reporting of the studies was low. Ambroxol is slightly more effective in relieving pain in acute sore throat than mint flavoured lozenges over a period of 3 h. However, the additional benefits of ambroxol beyond three hours, remain unclear given that more than 50% of patients using mint flavoured lozenges for pain relief reported good or very good efficacy after 1 day compared to 69% with ambroxol. Ambroxol is a safe option for individual patients with mainly local symptoms asking for treatment.

Синтез и местноанестезирующая активность новых производных ароилпировиноградных кислот

Ацилированием енаминоамидов ароилпировиноградных кислот получены хлориды N-{2-[((1Z)-1-{[(2,6-диметилфенил)амино]карбонил}-3-оксо-3-арилпроп-1-ен-1-ил)амино]этил}-N,N-диметил-1-оксоэтанаминиума. При исследовании их местноанестизирующего действия обнаружены соединения с высокой активностью.

The Trpa1 Agonist Cinnamaldehyde Acts as a Local Anesthetic Inhibiting Voltage-Gated Sodium Channels in Sensory Neurons

Cinnamaldehyde (CA) is a highly reactive compound that has been used in experimental models of neurogenic inflammation as specific agonist of the broadly tuned chemosensor TRPA1. In several models of chemonociception in mice and humans, we have found that CA only produces very weak avoidance, pain or visceral irritation responses. Furthermore, CA induces a dramatic decrease in the velocity of conduction and the amplitude of compound action potentials in the mouse tail. Noting the structural similarities between CA and classical local anesthetics, we investigated whether CA inhibits voltage-gated sodium channels (VGSC) expressed in sensory neurons. We found that CA inhibits TTX-sensitive voltage-dependent sodium currents in a concentration dependent manner in mouse trigeminal neurons with an IC50 of 1.5 mM. TTX-resistant sodium currents were inhibited with an IC50 of 0.8 mM. TTX-sensitive VGSC recorded in the immortalized DRG neuron-derived F11 cells were inhibited with an IC50 of 1.3 mM. CA modified the gating of TTX-sensitive sodium channels, inducing concentration-dependent shifts of the activation curve to depolarized voltages and shifts of the availability curve to more hyperpolarized voltages. In the presence of CA, the corresponding slope factors became significantly larger. CA-induced inhibition was enhanced at depolarized holding potentials. Inhibition of TTX-sensitive sodium channels was not frequency dependent and can occur when the channels are in resting/closed state(s). We conclude that CA inhibits VGSC in sensory neurons at concentrations that can be pharmacologically relevant, and that the mechanism of inhibition shares similarities with the action of local anesthetics.

Despite Differences in Cytosolic Calcium Regulation, Lidocaine Toxicity Is Similar in Adult and Neonatal Rat Dorsal Root Ganglia In Vitro

Neuraxial local anesthetics may have neurological complications thought to be due to neurotoxicity. A primary site of action of local anesthetics is the dorsal root ganglia (DRG) neuron. Physiologic differences have been noted between young and adult DRG neurons; hence, the authors examined whether there were any differences in lidocaine-induced changes in calcium and lidocaine toxicity in neonatal and adult rat DRG neurons. DRG neurons were cultured from postnatal day 7 (P7) and adult rats. Lidocaine-induced changes in cytosolic calcium were examined with the calcium indicator Fluo-4. Cells were incubated with varying concentrations of lidocaine and examined for viability using calcein AM and ethidium homodimer-1 staining. Live imaging of caspase-3/7 activation was performed after incubation with lidocaine. The mean KCl-induced calcium transient was greater in P7 neurons (P < 0.05), and lidocaine significantly inhibited KCl-induced calcium responses in both ages (P < 0.05). Frequency distribution histograms of KCl-evoked calcium increases were more heterogeneous in P7 than in adult neurons. With lidocaine, KCl-induced calcium transients in both ages became more homogeneous but remained different between the groups. Interestingly, cell viability was decreased by lidocaine in a dose-dependent manner similarly in both ages. Lidocaine treatment also activated caspase-3/7 in a dose- and time-dependent manner similarly in both ages. Despite physiological differences in P7 and adult DRG neurons, lidocaine cytotoxicity is similar in P7 and adult DRG neurons in vitro. Differences in lidocaine- and KCl-evoked calcium responses suggest the similarity in lidocaine cytotoxicity involves other actions in addition to lidocaine-evoked effects on cytosolic calcium responses.

Intrathecal Dexmedetomidine as Adjuvant for Bupivacaine in Subarachnoid Block for Lower Abdominal and Lower Limb surgeries

Context Spinal Anaesthesia is the most common anaesthetic technique used for lower abdominal and lower limb surgeries. Dexmedetomidine is a selective alpha agonist which is known to prolong the action of local anaesthetics when administered as an intravenous infusion or when administered 2 intrathecally.Aims To investigate the effect of intrathecal administration of dexmedetomidine on sensory motor block and haemodynamic parameters.Settings and Design Prospective Randomised Controlled Double Blind study. Methods and Material 100 patients were randomly allocated to two groups. Patients in Group N received 2ml of hyperbaric bupivacaine 1 ml normal saline and Group D received 2 ml of hyperbaric bupivacaine 5 mug dexmedetomidine in 1 ml normal saline.Statistical analysis used Paired Ttest Independent T test Chi square testResults Duration of sensory blockade was significantly prolonged in Group D 317.2plusmn 90.27 minutes when compared to Group N 204.26plusmn 84.77 minutes. The median cephalad level of sensory block achieved was T7 range -T5-T10 in group D and in group N it was T9 range - T6-T12. The regression of motor blockade to Bromage score 0 was significantly prolonged in Group D 323.14plusmn93.43 in comparison to Group N 206.98plusmn 88.Conclusion Intrathecal dexmedetomidine is an effective adjuvant and prolongs the duration of motor and sensory blockade with minimal side effects.

Local Anesthetics Induce Apoptosis in Human Breast Tumor Cells

Previous studies have shown that local anesthetics may induce apoptosis in some cell types. In this study, we investigated the apoptotic effects of local anesthetics in human breast tumor cells. Human breast cancer (MCF-7) and mammary epithelial (MCF-10A) cell lines were treated with lidocaine and/or bupivacaine. Cell viability, DNA fragmentation, and annexin V immunofluorescence staining were assessed. The effects on apoptosis-related protein expression were investigated by Western blot analysis. The findings were extended to studies in an in vivo xenograft model. Treatment of breast tumor cells with lidocaine and bupivacaine resulted in inhibition of cell viability via induction of apoptosis. The effects were more prominent in MCF-7 cells than in MCF-10A cells. Treatment with local anesthetics induced caspase 7, 8, 9, and poly ADP-ribose polymerase cleavage. The cleavage of caspase 7 and poly ADP-ribose polymerase induced by local anesthetics were effectively blocked by caspase inhibitors. Furthermore, treatment of MCF-7 xenografts with local anesthetics resulted in higher expression of cleaved caspase 7 and an increase in terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Lidocaine and bupivacaine induce apoptosis of breast tumor cells at clinically relevant concentrations. Our results reveal previously unrecognized beneficial actions of local anesthetics and call for further studies to assess the oncologic advantages of their use during breast cancer surgery.

The Effects of Dexmedetomidine Added to Spinal bupivacaine for lower limb surgery

Background: Intrathecal α2 agonists prolong the duration of action of local anesthetics and reduce the required dose. Dexmedetomidine is a α2 receptor agonist and its α2/α1 selectivity is 8 times higher than that of clonidine. Aims: In this study, we aimed to investigate the effect of adding dexmedetomidine to intrathecal bupivacaine on the onset time and duration of motor and sensory blocks. Methods: Patients were randomly assigned into two groups. Group B(n= 30) patients received 3ml (15mg) of 0.5% bupivacaine +0.5ml normal saline and Group BD (n= 30) patients received 3ml (15 mg) of 0.5% bupivacaine + 0.5ml (5μg) dexmedetomidine. The parameters studied were - onset and total duration of sensory block, onset and total duration of motor block, the most elevated dermatome level, hemodynamic alterations, and any intraoperative and postoperative complications. Results: The two groups were matched for demographic data. Sensory and motor block onset times were similar in both groups. The regression of the sensory block to S1 dermatome and regression of complete motor block were longer in Group BD than Group B (p<0.001). No significant difference were seen between the groups relative to the maximum level of sensory block (p=0.340). Statistically there were no significant differences in hemodynamic alterations and other adverse effects between the groups. Conclusion: We conclude that intrathecal dexmedetomidine addition to bupivacaine for spinal anaesthesia prolongs sensory and motor block durations without any significant adverse effects.

Exercise induced activation of sodium channels in augmentation of action of local anesthetics

Exercise induced activation of sodium channels in augmentation of action of local anesthetics

Finding the Route of Entry and Binding Site of Local Anaesthetics in Bacterial Voltage Gated Sodium Channels Using Molecular Dynamics Simulation

Voltage-gated sodium channels are proteins in cell membranes that initiate action potentials in neurons. Dysfunctional sodium channels are implicated in diseases such as chronic pain, epilepsy and cardiac arrhythmia, which are often treated by sodium channel blockers such as the family of local anaesthetics. These blockers can have adverse side-effects by blocking healthy channel subtypes, so researchers have strived to understand their mechanism of action to help design new, subtype-specific drugs. While there is no atomic resolution structural data on human sodium channels, the publication of a number of crystal structures of related, bacterial voltage-gated sodium channel in the last 2 years has offered the opportunity to explore the mechanism of entry and location of binding sodium channel blockers. Here, molecular dynamics simulations were used to determine the binding site of two channel blockers, benzocaine and phenytoin in the bacterial channel NavAb. We find that that binding involves nonspecific hydrophobic interaction in the channel lumen, relate this to measured binding affinities and speculate how sequence differences in this region could alter the affinity for anaesthetics. We also show the feasibility of drug entry from the membrane via the lateral fenestrations. By calculating the free energy for this process we show that these fenestrations are likely to represent the long postulated hydrophobic route of entry leading to tonic block of resting channels. While there are many differences between bacterial and human sodium channels, these results provide a first step in understanding the mechanism of action of local anaesthetics and can aid the rational search for subtype-specific drugs for use in mammalian sodium channels.

Development and in vitro evaluation of a novel contraceptive vaginal mucoadhesive propranolol hydrochloride film

Propranolol HCl is a s-adrenergic blocker that is used to treat cardiovascular disorders. This drug also possesses local anesthetic activity and is a potent inhibitor of human sperm motility. These characteristics give a potential to this drug for use as a vaginal contraceptive. The purpose of the study was to formulate and evaluate mucoadhesive vaginal films of propranolol hydrochloride. The formulations were prepared by the solvent-casting method; and were evaluated for their in vitro dissolution characteristics, in vitro mucoadhesive properties and their physico mechanical properties. From among all the developed formations, only formulation F20 (containing Eudragit RS PO 5.5 %, HPMC 150001 %), could release its drug over 12 h, with a burst release at the initial phase for providing an immediate contraceptive effect, followed by a sustained release pattern. This formulation also exhibited satisfactory mucoadhesive strength and residence time was selected as the final formulation for a novel mucoadhesive vaginal film.