Implications of Low-concentration Polymer on the Physical Stability of Glassy Griseofulvin: Role of the Segmental Mobility.

Crystallization of amorphous pharmaceutical solids are widely reported to be affected by the addition of polymer, while the underlying mechanism require deep study. Herein, crystal growth behaviors of glassy griseofulvin (GSF) doped with various 1% w/w polymer were systematically studied. From the molecular structure, GSF cannot form the hydrogen bonding interactions with the selected polymer poly(vinyl acetate), polyvinyl pyrrolidone (PVP), 60:40 vinyl pyrrolidone-vinyl acetate copolymer (PVP/VA 64), and poly(ethylene oxide) (PEO). 1% w/w polymer exhibited weak or no detectable effects on the glass transition temperature (Tg) of GSF. However, crystal growth rates of GSF was altered from 4.27-fold increase to 2.57-fold decrease at 8 ℃ below Tg of GSF. Interestingly, the ability to accelerate and inhibit the growth rates of GSF crystals correlated well with Tg of polymer, indicating the controlling role of segmental mobility of polymer. Moreover, ring-banded growth of GSF was observed in the polymer-doped systems. Normal compact bulk and ring-banded crystals of GSF were both characterized as the thermodynamically stable form I. More importantly, formation of ring-banded crystals of GSF can significantly weaken the inhibitory effects of polymer on the crystallization of glassy GSF.

Fast crystal growth of amorphous nimesulide: implication of surface effects.

Understanding crystallization behaviors is of utmost importance for developing robust amorphous pharmaceutical solids. Herein, the crystal growth behaviors of amorphous anti-inflammatory drug nimesulide (NIME) are systemically investigated in the glassy and supercooled liquid state as a function of temperature. A sudden over-tenfold increase is observed in the bulk crystal growth of NIME on cooling below its glass transition temperature (Tg). This fast growth behavior is known as a glass-to-crystal (GC) mode and has been reported in some molecular glasses. Fast surface crystal growth of NIME can persist up to Tg + 57°C with a weak jump in its growth rates at 30-40°C. In addition, surface crystal growth and GC growth of NIME exhibit an almost identical temperature dependence, supporting the view that GC growth is indeed a surface-facilitated process. Moreover, the bubble-induced fast crystal growth of NIME is observed in the interior of its supercooled liquid with approximately the same growth kinetics as surface crystal growth. These findings are relevant for a full understanding of the surface-related crystallization behaviors and physical stability of amorphous pharmaceutical formulations.

Formulation and characterisation of alginate hydrocolloid film dressing loaded with gallic acid for potential chronic wound healing.

Background: A dramatic growth in the prevalence of chronic wounds due to diabetes has represented serious global health care and economic issues. Hence, there is an imperative need to develop an effective and affordable wound dressing for chronic wounds. Recent research has featured the potential of bioactive compound gallic acid (GA) in the context of wound recovery due to their safety and comparatively low cost. However, there is a scarcity of research that focuses on formulating GA into a stable and functional hydrocolloid film dressing. Thus, this present study aimed to formulate and characterise GA-loaded alginate-based hydrocolloid film dressing which is potentially used as low to medium suppurating chronic wound treatment. Methods: The hydrocolloid composite films were pre-formulated by blending sodium alginate (SA) with different combinations of polymers. The hydrocolloid films were developed using solvent-casting method and the most satisfactory film formulation was further incorporated with various GA concentrations (0.1%, 0.5% and 1%). The drug-loaded films were then characterised for their physicochemical properties to assess their potential use as drug delivery systems for chronic wound treatment. Results: In the pre-formulation studies, sodium alginate-pectin (SA-PC) based hydrocolloid film was found to be the most satisfactory, for being homogenous and retaining smoothness on surface along with satisfactory film flexibility. The SA-PC film was chosen for further loading with GA in 0.1%, 0.5% and 1%. The characterisation studies revealed that all GA-loaded films possess superior wound dressing properties of acidic pH range (3.97-4.04), moderate viscosity (1600 mPa-s-3198 mPa-s), optimal  moisture vapor transmission rate (1195 g/m 2/day, 1237g/m 2/day and 1112 g/m 2/day), slower moisture absorption and film expansion rate and no chemical interaction between the GA and polymers under FTIR analysis. Conclusion: An SA-PC hydrocolloid film incorporated with gallic acid as a potentially applicable wound dressing for low to medium suppurating chronic wounds was successfully developed.

Moringa oleifera standardised aqueous leaf extract-loaded hydrocolloid film dressing: in vivo dermal safety and wound healing evaluation in STZ/HFD diabetic rat model.

Previously, Moringa oleifera leaf (MOL) standardised aqueous extract-loaded films were successfully developed and they showed potential wound healing activity in vitro. The objective of this study was to evaluate in vivo dermal safety as well as wound healing efficacy of these MOL film dressings (containing 0.1, 0.5 and 1% MOL) on diabetic rat model. The acute dermal toxicity was carried out on healthy rats, and signs of toxicity over 14 days were observed. For wound healing studies, excision and abrasion wounds were created out on the STZ/HFD-induced diabetic rat model and the wound healing was studied over 21 days. The wound healing evaluation determined by histology staining, hydroxyproline assay and ELISA assays on wound healing related-growth factors, cytokines and chemokines. MOL film formulations exhibited no signs of dermal toxicities. In excision wound model, 0.5% film significantly enhanced the wound closure by 77.67 ± 7.28% at day 7 compared to control group. While in abrasion wounds, 0.5% MOL films accelerated wound closure significantly at 81 ± 4.5% as compared to the control. The histology findings and hydroxyproline assay revealed that high collagen deposition and complete re-epithelialisation were observed for the wounds treated with 0.5 and 1% MOL films. All MOL film dressings had successfully tested non-toxic via in vivo safety dermal toxicity. It was concluded that the 0.5% MOL extract-loaded film had proven to be the most promising approach to accelerate diabetic wound healing process in both full-thickness excision and partial thickness abrasion wounds on the HFD/STZ-induced diabetic type II model.

Development and formulation of Moringa oleifera standardised leaf extract film dressing for wound healing application.

ETHNOPHARMACOLOGICAL RELEVANCE: M.oleifera is a medicinal plant traditionally used for skin sores, sore throat and eye infections. Recently, the wound healing property of the leaves of M. oleifera was has been well demonstrated experimentally in both in vivo and in vitro models. However, there is a lack of research which focuses on formulating M.oleifera into a functional wound dressing. In this study, the M.oleifera leaf standardized aqueous extract with highest potency in vitro migration was formulated into a film for wound healing application. MATERIALS AND METHODS: Firstly, M. oleifera leaf were extracted in various solvents (aqueous, 50%, 70% and 100% ethanolic extracts) and standardized by reference standards using UHPLC technique. The extracts were then tested for cell migration and proliferation using HDF and HEK cell lines. M. oleifera leaf aqueous extract was then incorporated into alginate-pectin (SA-PC) based film dressing. The film dressings were characterized for the physicochemical properties and the bioactives release from the M. oleifera leaf extract loaded film dressing was also investigated using Franz diffusion cells. RESULTS: All extracts were found to contain vicenin-2, chlorogenic acid, gallic acid, quercetin, kaempferol, rosmarinic acid and rutin. Among all M. oleifera extracts, aqueous standardized leaf extracts showed the highest human dermal fibroblast and human keratinocytes cells proliferation and migration properties. Among the film formulations, SA-PC (3% w/v) composite film dressing containing M. oleifera aqueous leaf extract was found to possess optimal physicochemical properties as wound dressing. CONCLUSION: A potentially applicable wound dressing formulated as an alginate-pectin film containing aqueous extracts of M. oleifera has been developed. The dressing would be suitable for wounds with moderate exudates.