Enhanced Drug Loading in the Drug-in-Adhesive Transdermal Patch Utilizing a Drug-Ionic Liquid Strategy: Insight into the Role of Ionic Hydrogen Bonding.

Though pharmaceutical polymers were widely used in inhibiting drug recrystallization via strong intermolecular hydrogen and ionic bonds, the improved drug stability was achieved at the cost of the drug release rate or amount in the drug-in-adhesive transdermal patch. To overcame the difficulty, this study aimed to increase drug loading utilizing a novel drug-ionic liquid (drug-IL) strategy and illustrate the underlying molecular mechanism. Here, naproxen (NPX) and triamylamine (TAA) were chosen as the model drug and corresponding counterion, respectively. In addiiton, carboxylic pressure-sensitive adhesive (PSA) was chosen as the model polymer. The drug-IL (NPX-TAA) was synthesized and characterized by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), and proton nuclear magnetic resonance. The miscibility between NPX-TAA and PSA was assessed using microscopy study, X-ray diffraction, fluorescence spectroscopy, and solubility parameter calculation. In addition, molecular mechanisms of crystallization inhibition were revealed by FT-IR, Raman spectroscopy, DSC, X-ray photoelectron spectroscopy (XPS), and molecular docking. Finally, the release pattern of the high load patch of NPX-TAA was evaluated using in vitro drug release and verified by a skin permeation experiment. The results showed that drug loading in PSA was increased by 5.0 times, which was caused by the synergistic effect of strong ionic hydrogen bonding (the decreased intensity and blue shift of the O-H peak of COOH in PSA) formed between NPX-TAA and PSA-COO- and normal hydrogen bonding (red shift of the C═O peak in PSA) formed between NPX-TAA and the carbonyl group of PSA. In addition, -NH+ of TAA was confirmed as the molecular basis of ionic hydrogen bonding through new peak appearance (binding energy: 400.0 eV) in XPS spectra. Moreover, high drug release percent (80.8 ± 1.8%) was achieved even at high drug loading compared with the control group (72.4 ± 2.2%). Thus, this study introduced an effective drug-IL method to enhance drug loading capacity and illustrated the brand-new action mechanism, which provided a powerful instrument for the development of a high drug loading-high release patch.

Spray drying of naproxen and naproxen sodium for improved tableting and dissolution - physicochemical characterization and compression performance.

In this work, the tabletability and dissolution of spray-dried forms of naproxen and its sodium salt were compared with those of unprocessed drugs. Solutions of naproxen or naproxen sodium alone or with HPMC (5% w/w of drug content) were spray dried. Scanning electron micrographs showed that naproxen sodium spray-dried particles were spherical, whereas those of naproxen were non-spherical but isodiametric. Powder x-ray diffraction and thermal analysis indicated that co-spray drying with HPMC resulted in reduced crystallinity of naproxen and higher naproxen sodium dihydrate content. FTIR and Raman analysis showed shifting, merging or elimination of bands in the spectra of the co-spray dried products signifying solid-state alterations. When mixed with suitable processing aids (7% w/w), all co-spray dried powders produced satisfactory tablets in the pressure range 73-295 MPa. Conversely, physical mixtures of naproxen compressed with the same aids failed tableting, whereas naproxen sodium produced weak tablets. Dissolution tests showed significant improvement for co-spray dried drugs tablets. Therefore, since the large therapeutic doses of naproxen and sodium naproxen limit the use of tableting aids, the improved compaction and dissolution performance of the spray-dried forms may be a formulation alternative.

Enhanced delivery of naproxen to the viable epidermis from an activated poly N-isopropylacrylamide (PNIPAM) Nanogel: Skin penetration, modulation of COX-2 expression and rat paw oedema.

Stimulus-responsive drug-loaded poly (N-isopropylacrylamide) nanogels were examined as a means of enhancing the delivery of naproxen into skin ex vivo. Following massaging into skin, the epidermis was probed (with and without base activation) for depth penetration and transdermal delivery of drug, and anti-inflammatory activity in the relative levels of COX-2 expression. Rat paw oedema testing was used to determine anti-inflammatory effects in vivo. When activated by sodium carbonate, particle size reduced by 19%. Tape stripping revealed significantly greater delivery of naproxen into the epidermis for the activated nanogel and the steady state flux was enhanced 2.8-fold. With base-activation COX-2 was 50% lower than non-activated, and this trend was confirmed by immunostaining, and by the reduction of rat paw swelling which provided ex vivo - in vivo corroboration. A mechanism of action is proposed. In conclusion, stimulus-responsive nanogels have potential for enhancing dermal drug delivery and therapeutic outcomes in inflammatory skin diseases.

Comparison of Clinical Efficacies of Preoperatively Initiated Naproxen Sodium-Codeine Phosphate in Combination, Diclofenac Potassium, and Benzydamine Hydrochloride for Pain, Edema, and Trismus After Extraction of Impacted Lower Third Molar: A Randomized Double-Blind Study.

PURPOSE: The aim of this study was to compare the clinical efficacies of naproxen sodium-codeine phosphate in combination, benzydamine hydrochloride, and diclofenac potassium for pain, edema, and trismus after lower third molar extraction. MATERIALS AND METHODS: Ninety healthy volunteers in whom impacted third molar extraction was indicated were randomly distributed into 3 groups. One hour before the tooth-extraction process, patients were administered one of the following drugs: naproxen sodium, 550 mg, and codeine phosphate, 30 mg, in a tablet; diclofenac potassium, 50 mg, in a coated pill; or benzydamine hydrochloride, 50 mg, in a coated pill. Pain assessment was conducted via a visual analog scale; edema assessment, by measuring the distances between predetermined facial landmarks; and trismus assessment, by measuring interincisal distance. Regarding rescue analgesics (paracetamol, 500 mg), the number and time of use by patients were recorded. RESULTS: Naproxen sodium-codeine phosphate was more effective for pain, edema, and trismus than diclofenac potassium and benzydamine hydrochloride (P < .05). Benzydamine hydrochloride yielded similar clinical responses to diclofenac potassium (P > .05). No drug-related side effects were observed. CONCLUSIONS: Naproxen sodium-codeine phosphate constitutes the drug of choice after the extraction of a patient's impacted lower third molar. Benzydamine hydrochloride has similar efficacy to diclofenac potassium, and it can be used as a nonsteroidal anti-inflammatory analgesic drug.

Impact of Polymer Type and Relative Humidity on the Long-Term Physical Stability of Amorphous Solid Dispersions.

The purpose of this work is to compare the long-term physical stability of amorphous solid dispersion (ASD) formulations based on three different commercially used excipients, namely, poly(vinylpyrrolidone) K25 (PVP), poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA64), and hydroxypropyl methylcellulose acetate succinate 126G (HPMCAS), at standardized ICH storage conditions, 25 °C/0% relative humidity (RH), 25 °C/60% RH, and 40 °C/75% RH. Acetaminophen (APAP) and naproxen (NAP) were used as active pharmaceutical ingredients (APIs). 18 month long stability studies of these formulations were analyzed and compared with the API/polymer phase diagrams, which were modeled and predicted by applying the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) and the Gordon-Taylor or Kwei equation. The study showed that, at dry storage, the solubility of the APIs in the polymers and the kinetic stabilizing ability of the polymers increase in the following order: HPMCAS < PVPVA64 < PVP. RH significantly reduces the kinetic stabilization as well as NAP solubility in the polymers, while the impact on APAP solubility is small. The impact of RH on the stability increases with increasing hydrophilicity of the pure polymers (HPMCAS < PVPVA64 < PVP). The experimental stability results were in very good agreement with predictions confirming that PC-SAFT and the Kwei equation are suitable predictive tools for determining appropriate ASD compositions and storage conditions to ensure long-term physical stability.

Photochemically Controlled Drug Dosing from a Polymeric Scaffold.

PURPOSE: To develop the first photoactive biomaterial coating capable of controlled drug dosing via inclusion of synthesised drug-3,5-dimethoxybenzoin (DMB) conjugates in a poly(2-methyoxyethyl acrylate) (pMEA) scaffold. METHODS: Flurbiprofen- and naproxen-DMB conjugates were prepared via esterification and characterised via NMR spectroscopy and mass spectrometry following chromatographic purification. Conjugate photolysis was investigated in acetonitrile solution and within the pMEA matrix following exposure to low-power 365 nm irradiation. Photo-liberation of drug from pMEA into phosphate buffered saline was monitored using UV-vis spectroscopy. RESULTS: The synthetic procedures yielded the desired drug conjugates with full supporting characterisation. Drug regeneration through photolysis of the synthesised conjugates was successful in both acetonitrile solution and within the pMEA scaffold upon UV irradiation. Conjugates were retained within the pMEA scaffold with exclusive drug liberation following irradiation and increased drug dose with increasing exposure. Multi-dosing capacity was demonstrated though the ability of successive irradiation periods to generate further bursts of drug. CONCLUSION: This study demonstrates the first application of photochemically controlled drug release from a biomaterial coating and the feasibility of using pMEA as a scaffold for housing the photoactive drug-DMB conjugates.

Novel organogels for topical delivery of naproxen: design, physicochemical characteristics and in vitro drug permeation.

Taking into account possible irritation of the skin upon contact with naproxen (NPX) crystals and lower bioavailability after administration of the suspended or ionized drug, the aim of the work was to design and characterize novel and easy-to-formulate gels with the entirely dissolved drug in the acidic form. The formulations contained ethanol, SynperonicTMPE/L 62 and Arlasolve® DMI or Transcutol®. Carbopol®940 was used as the thickener. The properties of organogels were compared with six market products. The rheological measurements included steady flow experiments and oscillatory analysis. The texture profile analysis was conducted to calculate the mechanistic parameters. The in vitro permeation studies were performed on SOTAX CE 7 smart apparatus with the application of Strat-M artificial membranes. The obtained organogels fulfilled the requirements for topical products in terms of consistency, uniformity, stability, drug dissolution and permeation. The permeation studies revealed distinct differences among the commercial hydrogels according to permeation coefficients (kP), drug flux (Jss) and average cumulative amount of NPX per area after 12 h (Q12h). The presented work clearly shows that the organogels can be proposed as an alternative for commercial products where NPX occurs in the form of crystals.

Native and microwave-modified Terminalia mantaly gums as sustained-release and bioadhesive excipients in naproxen matrix tablet formulations.

BACKGROUND: Hydrophilic polymers provide a means of sustaining drug delivery. Native gums may be limited in function, but modification may improve their activity. OBJECTIVES: The aim of the study was to evaluate native and modified forms of Terminalia mantaly gum for their sustained-release and bioadhesive properties. MATERIAL AND METHODS: The native gum (NTM) was modified by microwave irradiation for 20 seconds (MTM20) and 60 seconds (MTM60) and characterized using microscopy, Fourier transform infrared spectroscopy (FTIR) and packing properties. The effects of the thermally induced molecular reorientation were determined. Tablet formulations of naproxen were produced by direct compression. The mechanical, bioadhesive and release properties of the formulations were determined. RESULTS: Irradiation of NTM improved the gum's flow properties, resulting in Carr's Index and Hausner's ratios lower than 16% and 1.25, respectively. Swelling studies showed that MTM20 and MTM60 had lower water absorption capacity and swelling index values, while packing properties improved upon irradiation, as depicted by lower tapped density values. FTIR spectra of samples showed that the irradiated gums were distinct from the native gums and did not interact with naproxen sodium. The gum's mechanical properties improved with MTM20 and MTM60 and sustained-release action of up 12 h was obtained. CONCLUSIONS: Inclusion of hydroxypropyl methylcellulose (HPMC) in the tablet formulations proved critical for bioadhesion. Microwave irradiation of native Terminalia mantaly gum improved the flow, mechanical and sustained-release properties of Naproxen tablets, and the addition of HPMC increased bioadhesion properties. The tablet properties of the native gum were significantly improved after 20 s of microwave irradiation.

Formulation and in vitro evaluation of colchicines and naproxen sodium sustain release tablets in combination for treatment of gout.

Present investigation concern with combination of two drugs for the treatment of gout. One of these drug (naproxen sodium) is pain killer which is sustain their action within the body for 12 hours and the other drug (colchicine) is anti-gout, which release as conventional dosage. After oral administration naproxen will act as sustain release dosage and increase patient compliance about six batches of tablet were developed and evaluate .For the sustain release action polymers Methocel K4M and HPMCK15were used. These polymers were used in combination used with other inactive ingredients. Two methods were used for proration of final tablets. In 1st method only naproxen sodium granules were prepared which are sustained released. In second method these granules were mixed with colchicines powder and other all inactive ingredients. This method is easy and cost effective characterization of pallets and final tablets were performed. Final tablets were evaluated for all tests like appearance, friability, dissolution, hardness, assay, weight variation and in-vitro release study performed. The results obtained were satisfactory and complies with USP specification. Formulation containing combination of Methocel K4M and HPMC K15 showed good sustain release profile for 12 hours.

Efficacy and tolerability studies evaluating a sleep aid and analgesic combination of naproxen sodium and diphenhydramine in the dental impaction pain model in subjects with induced transient insomnia.

STUDY OBJECTIVES: The aim of this study was to evaluate the efficacy and tolerability of novel combination naproxen sodium (NS) and diphenhydramine (DPH) in subjects with postoperative dental pain along with transient insomnia induced by 5 h sleep phase advance. The present studies aimed to demonstrate the added benefit and optimal dosages of the combination product over individual ingredients alone in improving sleep and pain. METHODS: Each of the two studies was a two-centre, randomised, double-blind and double-dummy trial. In the first study, subjects were randomised into one of the following treatment arms: NS 440 mg/DPH 50 mg, NS 220 mg/DPH 50 mg, NS 440 mg or DPH 50 mg. In the second study, subjects received either NS 440 mg/DPH 25 mg, NS 440 mg or DPH 50 mg. The co-primary end-points in both studies were wake time after sleep onset (WASO) and sleep latency (SL) measured by actigraphy. Other secondary sleep and pain end-points were also assessed. RESULTS: The intent-to-treat population included 712 and 267 subjects from studies one and two, respectively. In the first study, only the NS 440 mg/DPH 50 mg combination showed significant improvements in both WASO vs. NS alone (-70.3 min p = 0.0002) and SL vs. DPH alone (25.50 and 41.50 min respectively, p < 0.0001). In the second study, the NS 440 mg/DPH 25 mg combination failed to show any significant improvements vs. either component alone. CONCLUSIONS: Only the NS 440 mg/DPH 50 mg combination demonstrated improvement in both sleep latency vs. DPH 50 mg and sleep maintenance (WASO) vs. NS 440 mg. There were no serious or unexpected adverse events reported in either study. CLINICAL TRIAL REGISTRATION: NCT01280591 (study 1); NCT01495858 (study 2).

Development of a solid self-microemulsifying drug delivery system (SMEDDS) for solubility enhancement of naproxen.

CONTEXT: Comparative evaluation of liquid and solid self-microemulsifying drug delivery systems (SMEDDS) as promising approaches for solubility enhancement. OBJECTIVE: The aim of this work was to develop, characterize, and evaluate a solid SMEDDS prepared via spray-drying of a liquid SMEDDS based on Gelucire® 44/14 to improve the solubility and dissolution rate of naproxen. MATERIAL AND METHODS: Various oils and co-surfactants in combination with Gelucire® 44/14 were evaluated during excipient selection study, solubility testing, and construction of (pseudo)ternary diagrams. The selected system was further evaluated for naproxen solubility, self-microemulsification ability, and in vitro dissolution of naproxen. In addition, its transformation into a solid SMEDDS by spray-drying using maltodextrin as a solid carrier was performed. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were used to evaluate the physical characteristics of the solid SMEDDS obtained. RESULTS: The selected formulation of SMEDDS was comprised of Miglyol 812®, Peceol™, Gelucire® 44/14, and Solutol® HS 15. The liquid and solid SMEDDS formed a microemulsion after dilution with comparable average droplet size and exhibited uniform droplet size distribution. In the solid SMEDDS, liquid SMEDDS was adsorbed onto the surface of maltodextrin and formed smooth granular particles with the encapsulated drug predominantly in a dissolved state and partially in an amorphous state. Overall, incorporation of naproxen in SMEDDS, either liquid or solid, resulted in improved solubility and dissolution rate compared to pure naproxen. CONCLUSION: This study indicates that a liquid and solid SMEDDS is a strategy for solubility enhancement in the future development of orally delivered dosage forms.

Taste masking of naproxen sodium granules by fluid-bed coating.

The taste of oral dosage forms is an important argument regarding patient's compliance and acceptability. For this reason, it is often necessary to mask an undesirable and unpleasant taste of an active pharmaceutical ingredient. The purpose of this study was to mask the taste of naproxen sodium by a new fluid-bed coating approach. Different compositions of coating suspensions were used to coat naproxen sodium granules. It was found that products with the addition of a plasticizer were not stable at 40 °C and tended to agglomerate. Subsequently, formulations without plasticizer were used and the ratio between water and Eudragit® E was varied. Increasing the fraction of water in the suspension from 3% to 14% reduced the effective release of naproxen sodium. An optimum ratio between naproxen sodium granules and Eudragit® E was found to be 1:1.576, where less naproxen sodium was released than the threshold bitter value and an appropriate taste masking for more than 5 min was guaranteed. Investigation of the particle size distribution revealed a d(10) of 138.35 ± 21.52 µm, a d(50 )= 256.40 ± 11.27 µm and a d(90 )= 500.85 ± 69.08 µm, which guarantees an acceptable mouthfeel for patients.

The impact of liposomes on transdermal permeation of naproxen--in vitro studies.

The possibility of applying liposomes as a topical drug delivery system is still a matter of intensive research. The purpose of this study was to determine the suitability of liposomes as carriers of naproxen and to prove their impact on the effectiveness of transdermal permeation of an active substance. The study was conducted with the use of Franz Diffusion Cell System by comparing the efficacy of a preparation containing 20% of phosphatidylcholine (PC) and 10% of naproxen with reference preparations, i.e., a formulation containing 10% of naproxen without PC and the commercial product Naproxen 10%, gel. The largest transdermal penetration flux of naproxen and the highest efficacy of naproxen permeation were obtained for the formulation containing 10% of naproxen and 20% of PC. The study of the influence of liposomes size and topology on the transdermal diffusion of naproxen (large unilamellar vesicle, LUV, multilamellar vesicle, MLV) showed that there was no statistically significant difference in the flux or total amounts of transdermally diffused naproxen between compared formulations. In conclusion, liposomes present in a formulation double the efficacy of the transdermal permeation of naproxen in vitro compared to reference preparations containing no carriers. Better permeation effect of a formulation was not related to the liposome type (LUV or MLV).

Unravelling the interactions between small molecules and liposomal bilayers via molecular dynamics and thermodynamic modelling.

Lipid-based drug delivery systems hold immense promise in addressing critical medical needs, from cancer and neurodegenerative diseases to infectious diseases. By encapsulating active pharmaceutical ingredients - ranging from small molecule drugs to proteins and nucleic acids - these nanocarriers enhance treatment efficacy and safety. However, their commercial success faces hurdles, such as the lack of a systematic design approach and the issues related to scalability and reproducibility. This work aims to provide insights into the drug-phospholipid interaction by combining molecular dynamic simulations and thermodynamic modelling techniques. In particular, we have made a connection between the structural properties of the drug-phospholipid system and the physicochemical performance of the drug-loaded liposomal nanoformulations. We have considered two prototypical drugs, felodipine (FEL) and naproxen (NPX), and one model hydrogenated soy phosphatidylcholine (HSPC) bilayer membrane. Molecular dynamic simulations revealed which regions within the phospholipid bilayers are most and least favoured by the drug molecules. NPX tends to reside at the water-phospholipid interface and is characterized by a lower free energy barrier for bilayer membrane permeation. Meanwhile, FEL prefers to sit within the hydrophobic tails of the phospholipids and is characterized by a higher free energy barrier for membrane permeation. Flory-Huggins thermodynamic modelling, small angle X-ray scattering, dynamic light scattering, TEM, and drug release studies of these liposomal nanoformulations confirmed this drug-phospholipid structural difference. The naproxen-phospholipid system has a lower free energy barrier for permeation, higher drug miscibility with the bilayer, larger liposomal nanoparticle size, and faster drug release in the aqueous medium than felodipine. We suggest that this combination of molecular dynamics and thermodynamics approach may offer a new tool for designing and developing lipid-based nanocarriers for unmet medical applications.

Analgesic eluting bone cement: A novel approach for targeted pain management in total knee arthroplasty - An in-vitro study.

BACKGROUND: The average rate of patient dissatisfaction following total knee arthroplasty (TKA) is 10%. Multi-modal analgesia is the present standard of pain management after TKA. Studies show that with multi-modal analgesia, approximately 60% of patients experience severe knee pain following surgery, while around 30% experience moderate pain. To date, there is no literature available on targeted pain management using bone cement. OBJECTIVES: To investigate the feasibility of incorporating anti-inflammatory medications and identify the analgesic with the best release pharmacokinetics from bone cement for application in pain management. METHODS: In an in-vitro study, 100 mg of five drugs (aceclofenac, diclofenac, naproxen, paracetamol and methyl prednisolone) were incorporated into bone cement (Palacos). Cement cubes holding each drug were made and allowed to harden for 30 min. Each drug-containing cube was placed in a beaker with saline for 72 h. Fractions of 10 ml were collected at 0, 6, 24, 48 and 72 h and analysed using high-pressure liquid chromatography to measure the percentage release of the drug from bone cement. RESULTS: Naproxen showed superior elution from bone cement, with 10.9% at 24 h and 9.08% at 72 h. Paracetamol showed 4.9% at 24 h and 3.78% at 72 h, aceclofenac 0.2% at 24 h and 0.4% at 72 h, diclofenac 3.03% at 24 h and 1.99% at 72 h, and methylprednisolone 0.26% at 24 h and 0.32% at 72 h. CONCLUSIONS: Polymethylmethacrylate bone cement can elute analgesics in vitro. Among the five drugs studied, naproxen had the best release kinematics from polymethylmethacrylate bone cement. Analgesic eluting bone cement is a novel approach for targeted postoperative pain management in TKA.

No need for rescue medication (NNR) as an easily interpretable efficacy outcome measure in analgesic trials: validation in an individual-patient meta-analysis of dental pain placebo-controlled trials of naproxen.

WHAT IS KNOWN AND OBJECTIVE: In analgesic trials, pain relief is often assessed using a pain-relief score. We aimed to assess, through a meta-analysis, whether absence of need for rescue medication (NNR) is a reliable outcome measure in the evaluation of acute pain relief. METHODS: Individual-patient meta-analysis of placebo-controlled trials of single-dose naproxen sodium 220 or 440 mg in dental pain. Efficacy estimates were based on NNR and compared with the more commonly used 50% maximum total pain relief score (50% TOTPAR). The trials included were the full set of trials sponsored by one manufacturer. RESULTS AND DISCUSSION: Need for rescue medication and 50% TOTPAR gave comparable estimates of efficacy of naproxen sodium (220 and 440 mg) relative to placebo in dental pain at both 8 and 12 h after dosing. WHAT IS NEW AND CONCLUSION: No need for rescue medication is a reliable outcome measure for use in acute pain trials. As it is more readily understandable than 50% TOTPAR, it should be the preferred primary outcome measure in acute pain trials.

Design, development, and optimization of polymeric based-colonic drug delivery system of naproxen.

The aim of present investigation deals with the development of time-dependent and pH sensitive press-coated tablets for colon specific drug delivery of naproxen. The core tablets were prepared by wet granulation method then press coated with hydroxypropyl cellulose (HPC) or Eudragit RSPO : RLPO mixture and further coated with Eudragit S-100 by dip immerse method. The in vitro drug release study was conducted in different dissolution media such as pH 1.2, 6.8, and 7.4 with or without rat caecal content to simulate GIT conditions. Surface morphology and cross-sectional view of the tablets were visualized by scanning electron microscopy (SEM). All prepared batches were in compliance with the pharmacopoeial standards. The tablets which are compression coated with HPC followed by Eudragit S-100 coated showed highest in vitro drug release of 98.10% in presence of rat caecal content. The SEM of tablets suggested that the number of pores got increased in pH 7.4 medium followed by dissolution of coating layer. The tablets coat erosion study suggested that the lag time depends upon the coating concentrations of polymers. A time-dependent hydrophilic polymer and pH sensitive polymer based press-coated tablets of naproxen were promising delivery for colon targeting.

Preparation and irradiation of Pluronic F127-based thermoreversible and mucoadhesive hydrogel for local delivery of naproxen.

To improve physical properties and modulate the mucoadhesive hydrogel formulation via cross-linking by radiation, hydrogels were prepared using thermoreversible polymer Pluronic F127 (PF127) and mucoadhesive polymer carbopol 934P (C934P). As a model drug, naproxen was loaded in the hydrogel formulation. Sol-gel transition temperatures of hydrogels were measured by the tube-inversion method. The mucoadhesive potential of each formulation was determined by measuring the force required to detach the formulation from oral mucosal tissue. To strengthen the mechanical properties, the formulations were irradiated using an electronic beam. Drug release from the hydrogels and the cytotoxicity of each formulation were investigated. Sol-gel transition temperatures of the formulations were decreased by the addition of carbopol and were close to body temperature. The mucoadhesive force of the PF127 formulation was increased by addition of carbopol. In vitro release was sustained and the release rate was reduced by the addition of carbopol. After irradiation, the mucoadhesive force was increased about five-fold especially in the case of PF127 23% (9.7 kPa) and in vitro release was not sustained further. In conclusion, the use of a PF127 formulation incorporating a mucoadhesive polymer could effectively and safely improve oral residence time and absorption of naproxen. Irradiated formulations showed permanent cross-linking and improved properties.

Effects of three oral analgesics on postoperative pain following root canal preparation: a controlled clinical trial.

AIM: To compare the effects of single doses of three oral medications on postoperative pain following instrumentation of root canals in teeth with irreversible pulpitis. METHODOLOGY: In this double-blind clinical trial, 100 patients who had anterior or premolar teeth with irreversible pulpitis without any signs and symptoms of acute or chronic apical periodontitis and moderate to severe pain were divided by balanced block random allocation into four groups of 25 each, a control group receiving a placebo medication, and three experimental groups receiving a single dose of either Tramadol (100 mg), Novafen (325 mg of paracetamol, 200 mg ibuprofen and 40 mg caffeine anhydrous) or Naproxen (500 mg) immediately after the first appointment where the pulp was removed, and the canals were fully prepared. The intensity of pain was scored based on 10-point VAS before and after treatment for up to 24 h postoperatively. Data were submitted to repeated analysis of variance. RESULTS: At the 6, 12 and 24 h postoperative intervals after drug administration, the intensity of pain was significantly lower in the experimental groups than in the placebo group (P < 0.01). Tramadol was significantly less effective (P < 0.05) than Naproxen, and Novafen that were similar to each other (P > 0.05). CONCLUSION: A single oral dose of Naproxen, Novafen and Tramadol taken immediately after treatment reduced postoperative pain following pulpectomy and root canal preparation of teeth with irreversible pulpitis.

Preparation, in vitro characterization and in vivo release of naproxen loaded in poly-caprolactone nanoparticles.

Naproxen was loaded in poly-caprolactone (PCL) nanoparticles as an implantable sustained release system to prolong its anti-inflammatory activity. Naproxen-loaded nanoparticles were produced with the following characteristics: Nanometric size (< 300 nm), negative zeta potential, low polydispersity index (< 0.1), satisfactory encapsulation efficiency, low water content (< 1%), and spherical shape. In vitro naproxen release profile was sustained and the kinetic followed the Higuchi model. The PCL nanoparticles containing about 12.5% (w/w) of the naproxen (sample A3) was chosen for complementary studies of stability and in vivo release in rats. Nanoparticles did not suffer alteration during stability studies. In vivo release was sustained by one month. Thus, nanoparticles showed potential to act as an implantable sustained release system for chronic inflammatory diseases use.