INHALED TASTE MASKED SPRAY DRIED KETOTIFEN MICROPARTICLES: FORMULATION, CHARACTERIZATION AND IN VITRO PULMONARY DEPOSITION

Objective: Preparation and characterization of inhalable taste masked microparticles (MPs) loaded with the anti-asthmatic bitter drug, ketotifen (KT).Methods: MPs were prepared by a spray-drying technique. The effects of addition of different excipients namely: mannitol, leucine and hyaluronic acid (HA) on the physicochemical properties of KT spray dried powders were determined. Powder taste was evaluated on volunteers. DSC and x-ray diffraction were done to investigate thermal and crystallographic properties of the powders. The surface morphology and shape of KT-loaded hyaluronic acid MPs were examined using scanning electron microscope, in vitro pulmonary deposition and inhalation indices were determined using a twin stage glass impinger (TSI).Results: Leucine improved the powder flow properties. Mannitol, at all tested ratios, produced brownish discoloration in spray dried powders (SDP) upon storage even in dessicator. At a drug to HA ratio of 1:2, the bitter taste of KT had significantly improved besides obtaining a high respirable particle fraction. This selected ratio showed good physicochemical stability for up to 9 mo.Conclusion: The developed KT spray dried particles may offer a good platform for the targeted pulmonary delivery of the drug overcoming the major biological barriers.Keywords: Ketotifen, Microparticles, Pulmonary delivery, Hyaluronic acid, Taste masking, Spray dryin

Determination of factors controlling the particle size and entrapment efficiency of noscapine in PEG/PLA nanoparticles using artificial neural networks

In this study, di- and triblock copolymers based on polyethylene glycol and polylactide were synthesized by ring-opening polymerization and characterized by proton nuclear magnetic resonance and gel permeation chromatography. Nanoparticles containing noscapine were prepared from these biodegradable and biocompatible copolymers using the nanoprecipitation method. The prepared nanoparticles were characterized for size and drug entrapment efficiency, and their morphology and size were checked by transmission electron microscopy imaging. Artificial neural networks were constructed and tested for their ability to predict particle size and entrapment efficiency of noscapine within the formed nanoparticles using different factors utilized in the preparation step, namely polymer molecular weight, ratio of polymer to drug, and number of blocks that make up the polymer. Using these networks, it was found that the polymer molecular weight has the greatest effect on particle size. On the other hand, polymer to drug ratio was found to be the most influential factor on drug entrapment efficiency. This study demonstrated the ability of artificial neural networks to predict not only the particle size of the formed nanoparticles but also the drug entrapment efficiency. This may have a great impact on the design of polyethylene glycol and polylactide-based copolymers, and can be used to customize the required target formulations

Cosm-nutraceutical nanovesicles for acne treatment : physicochemical characterization and exploratory clinical experimentation

The full exploration of the ‘nutraceuticals’ therapeutic potential in cosmetics has been hindered by their poor stratum corneum permeation. Therefore, the aim of the present study was to formulate a nutraceutical; quercetin, in novel vitamin C based nanovesicles (aspasomes), and to explore their beneficial effects in the treatment of acne. Aspasomes were characterized for their particle size, zeta potential, entrapment efficiency (EE%), 3-months storage stability, skin deposition/permeation, antioxidant potential, and morphology. Aspasomes antibacterial efficacy on 'Propionibacterium acnes' using the zone of inhibition assay was also tested, whilst their safety on skin fibroblastic cells was assessed in vitro using 3T3 CCL92 cell lines. An exploratory clinical trial was conducted in acne patients, and the percentage reduction of inflammatory, non-inflammatory and total acne lesions was taken as the evaluation criterion. Results revealed that quercetin-loaded aspasomes displayed a desirable nanometer size (125–184 nm), negative charge with good storage stability, and high skin deposition reaching 40%. Aspasomes managed to preserve the antioxidant activity of quercetin, and exhibited a significantly higher antibacterial effect (15 ± 1.53 mm) against 'Propionibacterium acnes' than quercetin alone (8.25 ± 2.08 mm), and were safe on skin fibroblastic cells. Upon clinical examination in 20 acne patients (14 females, 6 males), quercetin aspasomes exhibited reduction percentages of 77.9%, 11.8% and 55.3% for inflammatory lesions, comedones and total lesions respectively. This opens vast applications of the presented formulation in the treatment of other oxidative skin diseases, and delineates the nutraceuticals and nanoformulations prepared from natural materials as promising dermatological treatment modes

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely