SUSTAINED DELIVERY OF MOXIFLOXACIN FOR OCULAR APPLICATIONS.

Moxifloxacin is available as a marketed solution (Vigamox(R) which has to be administered 3 or more times a day leading to poor patient compliance and low ocular bioavailability. The overall goal of this research was to use formulation strategies and develop patient compliant dosage forms of moxifloxacin which are sustained-release so as to improve its retention and thereby ocular bioavailability. The first strategy that was explored was to develop sustained release inserts of moxifloxacin hydrochloride using hot-melt extrusion. The inserts showed sustained release and antibacterial activity up to 24h and could potentially be a once-a-day application and improve patient compliance Another strategy that was utilized was to develop a sustained release nanoemulsion of moxifloxacin with a mucoadhesive agent (HPMC or PVP) as a non-invasive, cost-effective alternative delivery system that is known to enhance the retention and permeation of drugs. The nanoemulsions were formulated with a lower amount of surfactant as compared to the nanoemulsion which is published in the literature (Shah et al., 2019), and were found to stable at room temperature for up to 45 days. The nanoemulsion was also filtered through various 0.22-micron filters and they did not show any significant change in physicochemical properties after filtration

Systematic screening of pharmaceutical polymers for hot melt extrusion processing: a comprehensive review

Pharmaceutical research, whether industrial or academic, has attempted to adopt approaches most efficient for the development of innovations. With the abundance of literature and growth of modern techniques available to minimize the number of trials, research is becoming more systematic by the day. Screening and selection of polymers for a pharmaceutical formulation can be challenging, considering the variety of polymers available and under development. Multiple considerations and experimentations are required to select a polymer to attain the target product profile. In this review, a stepwise discussion of techniques useful to screen and select polymers suitable for hot melt extrusion processing are explored and reported. First of all, selecting a range of polymers available for certain formulation types, for example, immediate release or modified release. Secondly, the screening of these selected polymers based on their physical and chemical properties as these properties should be in line with the active pharmaceutical ingredients (APIs) and the processing limitations of the equipment. Finally, selecting polymers using theoretical models such as solubility parameters and Flory Huggins modeling. Utilization of these three steps before proceeding to experimental methods will minimize the use of resources and provide a higher degree of accuracy towards the development of efficient, stable, and consistent products

Design of Topical Moxifloxacin Mucoadhesive Nanoemulsion for the Management of Ocular Bacterial Infections

Ocular bacterial infections can lead to serious visual disability without proper treatment. Moxifloxacin (MOX) has been approved by the US Food and Drug Administration as a monotherapy for ocular bacterial infections and is available commercially as an ophthalmic solution (0.5% w/v). However, precorneal retention, drainage, and low bioavailability remain the foremost challenges associated with current commercial eyedrops. With this study, we aimed to design a MOX-loaded nanoemulsion (NE; MOX-NE) with mucoadhesive agents (MOX-NEM) to sustain MOX release, as well as to overcome the potential drawbacks of the current commercial ophthalmic formulation. MOX-NE and MOX-NEM formulations were prepared by hot homogenization coupled with probe sonication technique and subsequently characterized. The lead formulations were further evaluated for in vitro release, ex vivo transcorneal permeation, sterilization, and antimicrobial efficacy studies. Commercial MOX ophthalmic solution was used as a control. The lead formulations showed the desired physicochemical properties and viscosity. All lead formulations showed sustained release profiles a period of more than 12 h. Filtered and autoclaved lead formulations were stable for one month (the last time point tested) under refrigeration and at room temperature. Ex vivo transcorneal permeation studies revealed a 2.1-fold improvement in MOX permeation of the lead MOX-NE formulation compared with Vigamox® eyedrops. However, MOX-NEM formulations showed similar flux and permeability coefficients to those of Vigamox® eyedrops. The lead formulations showed similar in vitro antibacterial activity as the commercial eyedrops and crude drug solution. Therefore, MOX-NE and MOX-NEM formulations could serve as effective delivery vehicles for MOX and could improve treatment outcomes in different ocular bacterial infections

Effect of surfactant concentration and sterilization process on intraocular pressure-lowering activity of Delta(9)-tetrahydrocannabinol-valine-hemisuccinate (NB1111) nanoemulsions

The use of Delta(9)-tetrahydrocannabinol (THC) and Delta(9)-tetrahydrocannabinol-valine-hemisuccinate (THC-VHS; NB1111) has recently been investigated in the management of intraocular pressure (IOP). The current study was undertaken to develop an optimized THC-VHS-loaded nanoemulsion formulation (NE; THC-VHS-NE) that could improve the drug load and duration of activity. THC-VHS-NE formulation was prepared by homogenization followed by ultrasonication. Sesame oil, Tween (R) 80, and Poloxamer (R) 188 were used as the oil, surfactant, and cosurfactant, respectively. Stability of the optimized THC-VHS-NE formulation was observed at 4 degrees C. The IOP lowering effect of the lead formulations, commercial timolol, and latanoprost ophthalmic solutions, as well as an emulsion in Tocrisolve (TM) (THC-VHS-TOC), was studied in New Zealand White rabbits following topical administration. The effect of surfactant concentration and sterilization process on IOP-lowering activity was also studied. THC-VHS-NE formulations (0.5, 1.0, and 2.0% w/v) showed dose dependent duration of action. The 1.0%w/v THC-VHS-NE formulation was selected for further evaluation because of its desirable physical and chemical characteristics. THC-VHS-NE formulation prepared with 2% w/v Tween (R) 80 exhibited a higher drop in IOP than the 0.75 and 4.0% w/v of Tween (R) 80 containing formulations. The IOP-lowering duration was, however, similar for the formulations with 0.75 and 2.0% Tween (R) 80, while that with 4.0% Tween (R) 80 was shorter. THC-VHS-NE formulation produced a greater drop in IOP (p < 0.05) and a longer duration of activity compared to THC-VHS-TOC, latanoprost, and timolol. The formulation could be sterilized by filtration without impacting product attributes. Overall, the optimized THC-VHS-NE formulation demonstrated a significantly better IOP reduction profile in the test model compared to the commercial ophthalmic solutions evaluated

Solid-State Stability Issues of Drugs in Transdermal Patch Formulations

The transdermal patch formulation has many advantages, including noninvasiveness, an ability to bypass the first-pass metabolism, low dosage requirements, and prolonged drug delivery. However, the instability of solid-state drugs is one of the most critical problems observed in transdermal patch products. Therefore, a well-characterized approach for counteracting stability problems in solid-state drugs is crucial for improving the performance of transdermal patch products. This review provides insight into the solid-state stability of drugs associated with transdermal patch products and offers a comprehensive update on the various approaches being used for improving the stability of the active pharmaceutical ingredients currently being used