The goal of this study was to develop and characterize an ion-activated in situ gel-forming estradiol (E2) solution eye drops intended for the prevention of age-related cataracts. Accordingly, in situ gelling eye drops were made using gellan gum as an ion-activated gel-forming polymer, polysorbate-80 as drug solubilizing agent, mannitol as tonicity agent, and combination of potassium sorbate and edetate disodium dihydrate (EDTA) as preservatives. The formulations were tested for the following characteristics: pH, clarity, osmolality, antimicrobial efficacy, rheological behavior, and in vitro drug release. Stability of the formulation was also monitored for 6 months at multiple storage conditions per ICH Q1A (R2) guidelines. The solution eye drops resulted in an in-situ phase change to gel-state when mixed with simulated tear fluid (STF). The gel structure formation was confirmed by viscoelastic measurements. Drug release from the gel followed non-fickian mechanism with 80% of drug released in 8 hr. The formulations were found to be clear, isotonic with suitable pH and viscoelastic behavior and stable at accelerated and long-term storage conditions for 6 months. In vitro results suggest that the developed formulation is suitable for further investigation in animal models to elucidate the ability of estrogen to prevent and delay cataracts.

The oral delivery of drugs with a narrow absorption window in the gastrointestinal tract (GIT) is often limited by poor bioavailability with conventional dosage forms due to incomplete drug release and short residence time at the site of absorption. To overcome this drawback and to maximize the oral absorption of these drugs, gastroretentive systems such as mucoadhesive, high-density, expandable, and floating systems have been developed. These systems provide controlled delivery of drugs with prolonged gastric residence time. However, in humans, differences in various physiological and biological factors can affect the gastric residence time and drug-delivery behavior from gastroretentive systems. Some floating drug-delivery systems (FDDS) have shown the capability to accommodate these variations without affecting drug release. This review mainly focuses on various physiological considerations for development of FDDS, and highlights recent technological developments including new dosage forms and their production techniques (e.g., holt-melt extrusion, melt pelletization, and pulsed plasma-irradiation processes). Alternatives to the existing in vitro compendial methods for evaluating floating dosage forms will be discussed, and a critical analysis of the existing literature on FDDS, identifying the potential areas for future research, is provided.

Abstract. The purpose of this research was to design oral controlled release (CR) matrix tablets of zidovudine (AZT) using hydroxypropyl methylcellulose (HPMC), ethyl cellulose (EC) and carbopol-971P (CP) and to study the effect of various formulation factors on in vitro drug release. Release studies were carried out using USP type 1 apparatus in 900 ml of dissolution media. Release kinetics were analyzed using zero-order, Higuchi's square root and Ritger-Peppas' empirical equations. Release rate decreased with increase in polymer proportion and compression force. The release rate was lesser in formulations prepared using CP (20%) as compared to HPMC (20%) as compared to EC (20%). No significant difference was observed in the effect of pH of dissolution media on drug release from formulations prepared using HPMC or EC, but significant difference was observed in CP based formulations. Decrease in agitation speed from 100 to 50 rpm decreased release rate from HPMC and CP formulations but no significant difference was observed in EC formulations. Mechanism of release was found to be dependent predominantly on diffusion of drug through the matrix than polymer relaxation incase of HPMC and EC formulations, while polymer relaxation had a dominating influence on drug release than diffusion incase of CP formulations. Designed CR tablets with pH independent drug release characteristics and an initial release of 17-25% in first hour and extending the release up to 16-20 h, can overcome the disadvantages associated with conventional tablets of AZT.