Novel Poly(vinylpyrrolidone)-Coated Silicone Contact Lenses to Improve Tear Volume During Lens Wear: In Vitro and In Vivo Studies.

Poly(vinylpyrrolidone) (PVP-K90) is widely used to manage dry eye syndrome (DES). The marketed eye drop solutions (high dose) need frequent instillation, affecting the routine lifestyle of patients. PVP-K90-laden contact lenses can be used to overcome the limitations of eye drop solutions (low bioavailability and frequent instillation). However, the conventional methods of PVP-K90 loading show poor loading capacity and short duration of effect. In the present study, we have developed PVP-K90-coated contact lenses via a short curing approach to increase the PVP-K90 loading capacity with a sustained release profile to manage dry eye syndrome. PVP-K90 was loaded by a soaking method (SM-PVP), direct loading (during fabrication, DL-PVP), a combination of soaking and direct loading (DL-SM-PVP), and a novel coating process (SM-PVP-C and DL-SM-PVP-C). The swelling studies suggested improvement in the water uptake (hydration) property of the contact lenses due to the presence of PVP-K90. The optical transparency was within an acceptable range. The in vitro release of PVP-K90 was in the following order: PVP-coated contact lens (168 h) > DL-SM-PVP (168 h) > DL-PVP (96 h) > SM-PVP (72-96 h). PVP-coated contact lenses showed a high burst effect (lubricating effect) and sustained release (3161-448 ng/h between 24 and 168 h) due to high PVP loading/coating in comparison to the uncoated respective contact lenses (964-113 ng/h between 24 and 96 h). In animal studies, the PVP-K90-coated contact lens showed higher tear volume in comparison to the respective uncoated contact lenses and an eye drop solution. This study demonstrates a novel approach of coating a high amount of PVP-K90 on contact lenses for sustained release to manage several ocular diseases like dry eye syndrome, conjunctivitis, and other ocular injuries.

Multiple drug delivery from the drug-implants-laden silicone contact lens: Addressing the issue of burst drug release.

A fixed combination of bimatoprost/timolol eye drop solution is used to manage the elevated intra-ocular pressure in glaucoma patients, including individuals whose condition is poorly controlled by monotherapy. Eye drop solutions are generally given in high dose, due to poor ocular bioavailability. The high ocular dose of bimatoprost and timolol lead to hyperaemia and systemic cardiac side effects respectively. Here, we introduce multiple implant-laden contact lenses (IM) to passively deliver timolol, bimatoprost and hyaluronic acid at therapeutically relevant doses without high burst release. The drug-loaded implants were individually implanted in the outer periphery of the silicone contact lenses. Atomic force microscopy showed the smooth surface of the implant contact lens, as the implants were inside the contact lens matrix. The implant lens (IM) showed major loss of drugs [timolol = 60.60%, bimatoprost = 61.75% and HA = 46.03%] during the monomer extraction and wet sterilization, while the option of dry radiation sterilization (IM-R lens) and hydration for 24 h prior to use showed relatively lower loss of drugs [timolol = 16.87%, bimatoprost = 47.95% and HA = 24.41%]. The in-vitro drugs release data of IM-R lens, showed sustained release for 72 h, with low burst release in comparison to the soaked (SM) and direct drug-laden contact lenses (DL). The in vivo drug release data in the rabbit tear fluid showed sustained release using IM-R lens in comparison to the SM lens and eye drop therapy. The burst release with the IM-R lens was many folds reduced, which could bypass the side effects associated with multiple eye drop therapy. The in vivo pharmacodynamic study in the rabbit model showed peak and valley profile with multiple eye drop therapy, while IM-R lens showed prolong reduction in intra ocular pressure (IOP) for 120 h. The study demonstrates the application of implantation technology to deliver multiple drug through contact lenses to treat glaucoma.

Lidocaine tripotassium phosphate complex laden microemulsion for prolonged local anaesthesia: In vitro and in vivo studies.

Lidocaine is widely used as a local anaesthetic in the clinical practice to manage pre- and post-operative pain, skin burns, etc. However, the short duration of action (< 2 h) of marketed dosage forms limit their ability to meet clinical needs. Herein, we prepared a lidocaine-tPP(tri potassium phosphate)-complex loaded microemulsion to achieve greater penetration, followed by destabilization of microemulsion in the skin layer to precipitate oil-complex to produce a depot effect in the skin for prolonging the effects of anaesthesia. The lidocaine-tPP-complex-microemulsion was compared with lidocaine base loaded microemulsion, marketed ointment USP and lidocaine HCl. The pseudo ternary phase diagrams at three Smix ratios (1:2, 1:3 and 1:4; Pluronic F127: PEG 400) were constructed using Capmul MCM C8 EP as oil phase. The Smix at 1:4 ratio showed large microemulsion area in comparison to 1:2 and 1:6 ratio. The lidocaine base (LD-1:4-ME10O45SM and LD-1:4-ME20O45SM) and lidocaine-tPP-complex (LDC-1:4-ME10O45SM and LDC-1:4-ME20O45SM) loaded microemulsion batches (1:4 ratio) were thermodynamically stable. The ex vivo diffusion study showed sustained release up to 12 h with microemulsion batches, in comparison to lidocaine HCl (4 h) and ointment base (7 h). The selected LDC-1:4-ME20O45SM batch was non-irritating on the rabbit skin. In drug retention studies, LD-1:4-ME20O45SM and LDC-1:4-ME20O45SM batches showed 2.68- and 3.93-fold greater lidocaine retention in comparison to ointment USP. The radiant heat tail-flick test showed prolong local anaesthesia using LDC-1:4-ME20O45SM in comparison to ointment USP. The findings suggest that lidocaine-tPP-complex loaded microemulsion could be a potential strategy for providing prolong local anaesthesia.

A simple high-performance liquid chromatographic method for the estimation of boswellic acids from the market formulations containing Boswellia serrata extract.

A simple, rapid, and reproducible reverse-phase high-performance liquid chromatographic method is developed for the estimation of boswellic acids, the active constituents in Boswellia serrata oleo-gum resin. The chromatographic separation is performed using a mobile phase consisting of acetonitrile-water (90:10, % v/v) adjusted to pH 4 with glacial acetic acid on a Kromasil 100 C18 analytical column with flow rate of 2.0 mL/min and detection at 260 nm. The elution times are 4.30 and 7.11 min for 11-keto beta-boswellic acid (11-KBA) and 3-acetyl 11-keto beta-boswellic acid (A-11-KBA), respectively. The calibration curve is linear in the 11.66-58.30 microg/mL and 6.50-32.50 microg/mL range for 11-KBA and A-11-KBA, respectively. The limits of detection are 2.33 microg/mL and 1.30 microg/mL for 11-KBA and A-11-KBA, respectively. The mean recoveries are 98.24% to 104.17% and 94.12% to 105.92% for 11-KBA and A-11-KBA, respectively. The inter- and intra-day variation coefficients are less than 5%. The present method is successfully applied for the estimation of boswellic acids from the market formulations containing Boswellia serrata extract.

Estimation of boswellic acids from market formulations of Boswellia serrata extract and 11-keto beta-boswellic acid in human plasma by high-performance thin-layer chromatography.

A rapid and sensitive high-performance thin-layer chromatographic (HPTLC) method was developed and validated for the quantitative estimation of boswellic acids in formulation containing Boswellia serrata extract (BSE) and 11-keto beta-boswellic acid in human plasma. Simple extraction method was used for isolation of boswellic acid from formulation sample and acidified plasma sample. The isolated samples were chromatographed on silica gel 60F(254)-TLC plates, developed using ternary-solvent system (hexane-chloroform-methanol, 5:5:0.5, v/v) and scanned at 260 nm. The linearity range for 11-KBA spiked in 1 ml of plasma was 29.15-145.75 ng with average recovery of 91.66%. The limit of detection and limit of quantification for 11-KBA in human plasma were found to be 8.75 ng/ml and 29.15 ng/ml. The developed method was successfully applied for the assay of market formulations containing BSE and to determine plasma level of 11-keto beta-boswellic acid in a clinical pilot study.