PREPARATION AND CHARACTERIZATION OF POLY (VINYL ALCOHOL)–POLY (VINYL PYRROLIDONE) MUCOADHESIVE BUCCAL PATCHES FOR DELIVERY OF LIDOCAINE HCL

Objective: The objectives of this study were to prepare and characterize a buccal mucoadhesive patch using poly (vinyl alcohol) (PVA), poly (vinyl pyrrolidone) (PVP) as a mucoadhesive matrix, Eudragit S100 as a backing layer, and lidocaine HCl as a model drug.Methods: Lidocaine HCl buccal patches were prepared using double casting technique. Molecular interactions in the polymer matrices were studied using attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC) and X-ray diffractometry. Mechanical and mucoadhesive properties were measured using texture analyzer. In vitro permeation of lidocaine HCl from the patch was conducted using Franz diffusion cell.Results: Both of the free and lidocaine HCl patches were smooth and transparent, with good flexibility and strength. ATR-FTIR, DSC and X-ray diffractometry studies confirmed the interaction of PVA and PVP. Mechanical properties of matrices containing 60% PVP were significantly lower than those containing 20% PVP (*P<0.05). Mucoadhesive properties had a tendency to decrease with the concentration of PVP in the patch. The patch containing 60% PVP had significantly lower muco-adhesiveness than those containing 20% PVP (*P<0.05). In vitro permeation revealed that the pattern of lidocaine HCl permeation started with an initial fast permeation, followed by a slower permeation rate. The initial permeation fluxes follow the zero-order model of which rate was not affected by the PVP concentrations in the PVA/PVP matrix.Conclusion: Mucoadhesive buccal patches fabricated with PVA/PVP were successfully prepared. Incorporation of PVP in PVA/PVP matrix affected the strength of polymeric matrix and mucoadhesive property of patches

PREPARATION AND CHARACTERIZATION OF GRAPEFRUIT OIL BASE MICROEMULSIONS OF CAFFEINE

Objective: The objective of the present work was to prepare and characterize grapefruit oil base microemulsions loaded with caffeine as a model hydrophilic compound. Methods: The formulation ingredients were selected based on surfactant efficiency and solubility studies. Ternary phase diagrams of grapefruit oil were constructed using the water titration method. Nine O/W microemulsions were constructed and prepared by mixing surfactant system, grapefruit oil, water and caffeine together. The resulting microemulsions were investigated for viscosity using Brookfield viscometer, for pH value using a digital pH meter, and for average particle size and polydispersity index (PDI) using a Zetasizer Nano. Ex vivo skin permeation through porcine ear skin was conducted using a side-by-side diffusion cell. The amount of caffeine was analyzed using HPLC-UV method. Results: Tween 20 yielded the highest emulsification ability for grapefruit oil and the highest caffeine solubility. It was selected as a major surfactant. Caffeine was slightly soluble in ethanol and isopropyl alcohol, but sparingly soluble in propylene glycol (PG). These ingredients were used as the cosurfactants. Nine grapefruit oil base microemulsions were prepared and characterized. The pH of microemulsions was within the range of 4.48-5.96. Particle size was in the range of 10.81±0.03 to 62.18±21.04 µm with the PDI of 0.13±0.02 to 0.64±0.11. Viscosity and particle size of microemulsions increased significantly with increasing grapefruit oil or tween 20 content. Addition of PG as cosurfactant resulted in the increases of viscosity, particle size and PDI. Depending on the formulation parameters, the permeation fluxes of caffeine from grapefruit oil base microemulsions were in the range of 28.4±3.4-361.4±15.2 µg/cm2/h. Conclusion: The grapefruit oil base microemulsions were successfully formulated. The physical properties and caffeine permeation of these microemulsions were found to be dependent on the grapefruit oil content, tween 20 content, cosurfactant type and content, as well as caffeine loading. The optimal formulation of grapefruit oil base microemulsion suggested composition of 5% grapefruit oil, 50% surfactant system (tween 20 and ethanol at the ratio of 9:1), and water

EFFECTS OF FORMULATION PARAMETERS ON PROPERTIES OF GASTRIC FLOATING TABLETS CONTAINING POORLY SOLUBLE DRUG: DICLOFENAC SODIUM

Objective: The objective of this study was to prepare and investigate the effects of formulation parameters on the properties of gastric floating tablets containing diclofenac sodium (DICL) as a model of poorly soluble acidic drug, sodium bicarbonate (NaHCO3) or calcium carbonate (CaCO3) as gas-forming agent, hydroxypropyl methylcellulose (HPMC) K100M or K15M as swelling polymer and sodium lauryl sulfate (SLS) as wetting agent.Methods: DICL floating tablets were prepared using direct compression method. The compressed tablets were evaluated for tablet properties, swelling index, and in vitro buoyancy. The in vitro release under non-sink condition was determined. Molecular interaction was studied using differential scanning calorimetry and fourier transform infrared spectroscopy.Results: The tablet properties of all DICL floating tablets were within the acceptance criteria. The molecular interaction between DICL and excipients in the formulation was excluded. Depends on the formulation compositions, the swelling index at 3 h (SI) ranged from 44±11 to 1158±33 %, whereas the buoyancy properties namely floating lag time (FLT) and total floating time (TFT) were 0.33±0.03 to 10.04±0.04 min and 10.0±0.0 to>12 h, respectively. NaHCO3 showed higher swelling, buoyancy and release properties compared to those of CaCO3. NaHCO3 at 20% gave sufficient swelling (SI of 1074±16 %), buoyancy (FLT of 0.39±0.03 min, TFT of>12 h) and release properties (cumulative release of 5.83±0.02 %). HPMC K100M showed better swelling property of which its initial swelling rate was 1412±25 %/h compared to HPMC K15M (1042±31 %/h). HPMC K100M at 20% showed better buoyancy and release properties compared to those obtained from HPMC K100M at 30%. The release testing under non-sink conditions was able to distinguish the effect of formulation parameters on the DICL release profiles. Incorporation of SLS at 0.25% could enhance both release rate and cumulative release of DICL from the floating tablets. Nevertheless, it showed the unacceptable adverse effect on swelling and buoyancy properties of DICL floating tablets. The TFT of DICL floating tablets containing 0.25% SLS was only 0.5±0.0 h.Conclusion: DICL floating tablets were successfully prepared. Tablets possessing suitable swelling and buoyancy properties were obtained using NaHCO3 at 20% as a gas-forming agent, with HPMC K100M at 10 and 20% as floating matrix and swelling polymer. Addition of SLS as wetting and solubilizing agent showed the unacceptable adverse effect on the swelling and buoyancy properties of DICL floating tablets. The release under sink conditions and/or in vivo pharmacokinetic studies shall be further performed

DEVELOPMENT OF HERBAL CAPSULES CONTAINING MULBERRY LEAF AND BLACK TEA EXTRACTS USING THE MODIFIED LIQUISOLID TECHNIQUES

Objective: The objective of this study was to develop the capsules containing mulberry leaf extract (MLE) and black tea extract (BTE). Methods: MLE and BTE were prepared by maceration and determined for phytochemicals, in vitro alpha-amylase and alpha-glucosidase inhibitory activities using the enzymatic colorimetric assay. The granules of MLE and BTE were prepared by the application of liquisolid technique and evaluated for the flow properties. The selected granule formulation was filled into the hard gelatin capsule and evaluated for weight variation and disintegration. Results: The yields of MLE and BTE solid extracts were 8.12 and 4.23% w/w, respectively. Total phenolic and total flavonoid contents were 32.46±5.22 mg TAE/g DW and 44.03±3.37 mg QE/g DW for MLE and 244.66±23.28 mg TAE/g DW and 214.43±3.22 mg QE/g DW for BTE, respectively. The IC50 for alpha-amylase of MLE and BTE were 0.69±0.04 and 3.34±0.08 mg/ml, respectively; whereas those for alpha-glucosidase of MLE and BTE were 0.67±0.42 and 0.43±0.15 mg/ml, respectively. The granule prepared with MCC and silica at the ratio of 20:1 showed the highest flowability. The weight variation of the prepared MLE and BTE capsules was within the range of the limitation criteria of ±5%. The average disintegration time of capsules was 1.1±0.1 min. Conclusion: Herbal capsules of MLE and BTE were successfully prepared. The suitable carrier and coating were MCC and silica with a ratio of 20:1. This study revealed the potential application of liquisolid technique as a tool to produce a capsule of herbal crude extracts

DEVELOPMENT OF SEMISOLID PREPARATIONS CONTAINING EXTRACT OF THAI POLYHERBAL RECIPE FOR ANTI-INFLAMMATORY EFFECT

Objective: The objective was to develop the semisolid preparations containing extract of Thai polyherbal recipe with anti-inflammatory effect. Methods: Polyherbal ethanolic extract was prepared by maceration and determined for phytochemicals and antioxidant activity. Effects of extract on the production of pro-inflammatory mediator-nitric oxide (NO)-were examined in RAW 264.7 cells. Semisolid preparations, balm, and gel, were prepared and evaluated. In vitro release profiles and mechanisms of phenolic compounds, phytochemical markers, from the preparations were investigated. Results: Polyherbal ethanolic extract was dark yellow-green, viscous liquid with the yields of 8.2%. Total phenolic and total flavonoid contents were 121.21±1.60 mg GAE/g and 26.55±1.38 mg QE/g, respectively. Antioxidant assay showed that polyherbal extract can scavenge the radical to a certain extent, with DPPH IC50 of 160.75±3.43 µg/ml and FRAP values of 91.94±4.17 mg FeSO4/g. In vitro anti-inflammatory test revealed that the extract inhibited NO production in a dose-dependent manner, with IC50 of 145.65±3.26 µg/ml. The yellowish-green color, homogenous and suitable for skin application polyherbal balm and gel was obtained. The higher release of phenolics from the gel was observed, with the cumulative release at 8 h of 119.0±4.3 mg GAE, whereas that from the balm was only 39.7±2.0 mg GAE. The phenolic release profile was found to be best fitted with the Higuchi model. Conclusion: The semisolid preparations containing Thai polyherbal recipe extract with anti-inflammatory effect were successfully prepared. The proper semisolid base and compositions are crucial for effective skin delivery as they influence the release rates of phytochemical markers

In Vitro Release, Mucosal Permeation and Deposition of Cannabidiol from Liquisolid Systems: The Influence of Liquid Vehicles

This work investigated the influence of liquid vehicles on the release, mucosal permeation and deposition of cannabidiol (CBD) from liquisolid systems. Various vehicles, including EtOH, nonvolatile low- and semi-polar solvents, and liquid surfactants, were investigated. The CBD solution was converted into free-flowing powder using carrier (microcrystalline cellulose) and coating materials (colloidal silica). A physical mixture of the CBD and carrier–coating materials was prepared as a control. The non-crystalline state of CBD in the liquisolid systems was confirmed using XRD, FTIR and SEM studies. The CBD liquisolid powder prepared with volatile and nonvolatile solvents had a better CBD release performance than the CBD formed as the surfactant-based and control powders. The liquisolid systems provided the CBD permeation flux through porcine esophageal mucosa ranging from 0.68 ± 0.11 to 13.68 ± 0.74 µg·cm−2·h−1, with the CBD deposition levels of 0.74 ± 0.04 to 2.62 ± 0.30 μg/mg for the dry mucosa. Diethylene glycol monoethyl ether showed significant CBD permeation enhancement (2.1 folds) without an increase in mucosal deposition, while the surfactants retarded the permeation (6.7–9.0 folds) and deposition (1.5–3.2 folds) significantly. In conclusion, besides the drug release, liquid vehicles significantly influence mucosal permeation and deposition, either enhanced or suppressed, in liquisolid systems. Special attention must be paid to the selection and screening of suitable liquid vehicles for liquisolid systems designed for transmucosal applications

Preparation and Evaluation of Directly Compressible Orally Disintegrating Tablets of Cannabidiol Formulated Using Liquisolid Technique

This study demonstrated the implementation of a liquisolid technique to formulate directly compressible orally disintegrating tablets (ODTs). Cannabidiol (CBD), a hydrophobic cannabinoid, was prepared as a liquisolid powder using microcrystalline cellulose–colloidal silicon dioxide as a carrier–coating material. Different liquid vehicles differing in their volatility, hydrophilicity, and viscosity were investigated. Each of the CBD–ODTs comprised CBD liquisolid powder (10 mg CBD), superdisintegrant, flavors, lubricant, and filler. The physical mixture (PM) ODT was prepared as a control. Ethanol-based ODTs (CBD–EtOH–ODTs) had comparable tablet properties and stability to CBD–PM–ODTs. ODTs with nonvolatile-vehicle-based liquisolid powder had lower friability but longer disintegration times as compared with CBD–PM–ODTs and CBD–EtOH–ODTs. Compression pressure influenced the thickness, hardness, friability, and disintegration of the ODTs. With a suitable compression pressure to yield 31-N-hardness-ODTs and superdisintegrant (4–8%), CBD–ODTs passed the friability test and promptly disintegrated (≤25 s). Times to dissolve 50% of CBD–PM–ODTs, CBD–EtOH–ODTs, and nonvolatile-vehicle-based CBD–ODTs were 10.1 ± 0.7, 3.8 ± 0.2, and 4.2 ± 0.4–5.0 ± 0.1 min, respectively. CBD–EtOH–ODTs exhibited the highest dissolution efficiency of 93.5 ± 2.6%. Long-term and accelerated storage indicated excellent stability in terms of tablet properties and dissolution. Nonvolatile-vehicle-based CBD–ODTs exhibited a higher percentage of remaining CBD. This study provides useful basic information for the development of ODT formulations using a liquisolid technique application

Formulation and In Vitro Evaluation of Mucoadhesive Sustained Release Gels of Phytoestrogen Diarylheptanoids from <i>Curcuma comosa</i> for Vaginal Delivery

Diarylheptanoids (DAs) characterized by a 1,7-diphenylheptane structural skeleton are considered a novel class of phytoestrogens. The DAs available in Curcuma comosa Roxb. (C. comosa) extract demonstrated significant estrogenic activities both in vitro and in vivo. This study aimed to develop and comprehensively evaluate a mucoadhesive vaginal gel for the sustained release of DAs. Different mucoadhesive polymers as gelling agents were investigated. C. comosa ethanolic crude extract was used as a source of DAs. All C. comosa gels were light brown homogeneous with pH within 4.4–4.6. Their flow behaviors were pseudoplastic with a flow behavior index of 0.18–0.38. The viscosity at a low shear rate varied from 6.2 to 335.4 Pa·s. Their mechanical and extrudability properties were associated well with rheological properties. Polycarbophil (PCP):hydroxypropyl methylcellulose (HPMC) blends had a higher mucoadhesiveness to porcine vaginal mucosa than those of PCP-based or HPMC-based gels. All C. comosa gels exhibited a sustained, zero-order DA release pattern over 72 h. Korsmeyer and Peppas equation fitting indicated a non-Fickian, case II transport release mechanism. C. comosa gels had good physical and chemical stability under low-temperature storage for up to 12 months. PCP:HPMC-based mucoadhesive gels could be a proper delivery system for vaginal administration of DAs

Sodium Alginate-Quaternary Polymethacrylate Composites: Characterization of Dispersions and Calcium Ion Cross-Linked Gel Beads

The objective of this work was to examine the effect of quaternary polymethacrylate (QPM), a water-insoluble polymer with a positive charge, on the characteristics of the sodium alginate (SA) dispersions and the calcium alginate (CA) gel beads containing propranolol HCl (PPN). The SA-QPM composite dispersions presented the formation of flocculates with a negative charge due to the electrostatic interaction of both substances. The QPM addition did not affect the SA dispersions&rsquo; Newtonian flow, but the composite dispersions&rsquo; viscosity enhancement was found. The PPN-loaded CA-QPM gel beads had more spherical than the PPN-loaded CA gel beads. The incorporation of QPM caused a bigger particle size, higher drug entrapment efficiency, and greater particle strength of the gel beads. Despite the similar water uptake property, the PPN-loaded CA-QPM gel beads displayed lower burst release and slower drug release rate than the PPN-loaded CA gel beads. However, the drug release from the PPN-loaded CA-QPM gel beads involved drug diffusion and matrix swelling mechanisms. This study demonstrated that adding QPM into the SA dispersions leads to a viscosity synergism. The CA-QPM gel beads display a good potential for use as a bioactive compound delivery system