Preparation, characterization, and antibacterial activity of plaunotol and plaunoi extracts complexed with hydroxypropyl-ß-cyclodextrin.

Croton stellatopilosus (Plaunoi) leaves accumulate several diterpenes and possess various pharmacological activities. The present study aimed to prepare, characterize and assess the antibacterial activity of inclusion complexes prepared by mixing plaunotol (PL) or plaunoi extract (PE) with cyclodextrins (CD), including α-CD, ß-CD, γ-CD, and hydroxypropyl-ß-cyclodextrin (HP-ß-CD). The inclusion complexes were characterized using SEM, XRD, DSC, and FT-IR and evaluated for aqueous solubility and thermal stability. The PL and PE lyophilized complexes with HP-ß-CD were further evaluated for their antibacterial activity against acne-causing bacteria. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of PL, PE, and the inclusion complexes evaluated using the agar dilution method revealed that the MIC and MBC values of the inclusion complexes were lower than those of PL or PE alone. Interestingly, the complexes had a synergistic activity with clindamycin after testing with checkerboard assay. The hydrogel containing the inclusion complex and clindamycin were assessed for antibacterial activity using the agar well diffusion method. The results indicated that the hydrogels showed significant inhibition of bacterial growth. In conclusion, the prepared solid dispersion of PL or PE with HP-ß-CD could enhance antibacterial activity by increasing the drug solubility. The hydrogels containing PL or PE complex and clindamycin could be considered as a candidate for the treatment of acne vulgaris.

Characterization, Antioxidant and Antibacterial Potentials of Tamarindus indica L. Fruit Pulp Extract Loaded O/W Nanoemulsions

Abstract The main purposes of the current study were to formulate o/w nanoemulsions as a carrier for Tamarindus indica (tamarind) fruit pulp extract and to study the antioxidant and antibacterial potentials of nanoemulsions containing tamarind extract, focusing on cosmetic/hygiene applications. The o/w nanoemulsions using a mixture of Tween 80 and Span 80 as an emulsifier (5%w/w) were prepared by a high pressure homogenization process. Two concentrations of sweet tamarind extract, 3.3 and 6.6%w/w, based on the bioactivity study, were incorporated into the blank nanoemulsions to produce loaded nanoemulsions, F1-3.3TE (3.3%) and F1- 6.6TE (6.6%). As compared with the unloaded nanoemulsion, both tamarind extract loaded nanoemulsions showed reduced pH and significantly increased viscosity. Overall, the loaded nanoemulsions had droplet sizes of approximately 130 nm, zeta potential around -38 mV and polydispersity index (PDI) values less than 0.2. The nanoemulsion F1-3.3TE had better stability (e.g. significantly greater % tartaric acid content and lesser PDI value) than the nanoemulsion F1-6.6TE did. The antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl assay revealed that the nanoemulsions F1-3.3TE and F1-6.6TE had scavenging activities of 81.66 ± 0.77% and 63.80 ± 0.79%, respectively. However, antioxidant activity of these two formulations decreased under stress conditions (heating-cooling cycles). Such incidence did not occur for their antibacterial properties investigated by agar well diffusion technique. The two formulations exhibited inhibition zones of approximately 24.0-27.7 mm against Staphylococcus aureus and Staphylococcus epidermidis, responsible for malodor of underarms. The results suggest the potential of using sweet tamarind pulp extract loaded nanoemulsions as hygiene products.

RiceSorb® as Talcum Substitute for Loose Face Powders: Formulation and Characterization.

Excessive and daily inhalation of talcum, a main ingredient of face powders, causes pulmonary talcosis, which has led to the replacement of talcum with safer natural ingredients. RiceSorb®, or Oryza sativa starch from Japanese rice, was used as an alternative owing to its nontoxic and excellent oil absorption capacity. The objectives of the present work were to formulate loose face powders from RiceSorb® and to investigate the physicochemical properties of the prepared formulations. Five formulations of loose face powders were prepared by varying the ratios between talcum and RiceSorb®: 4:0 (FT0), 3:1 (FT1), 1:1 (FT2), 1:3 (FT3), and 0:4 (FT4). The physicochemical properties were evaluated mainly based on USP 41 and NF 36 such as morphology by using a scanning electron microscope, bulk density, flow property (angle of repose), moisture content (MC), and pH. The stability of the formulations were also performed at ambient temperature and 45°C for 2 months. The formulations had pH 6.90-8.62, bulk density 0.33-0.49 g/ml, and an angle of repose 30°-41°. Overall, the formulations which contained only RiceSorb® (FT4) or higher proportion of RiceSorb® (FT3) had finer particles, lower bulk density, pH, and angle of repose than those of the formulations containing high proportion of talcum: FT0 and FT1. Under storage conditions for 2 months, the formulations containing high proportion of RiceSorb® exhibited noticeably increased MC and angle of repose. However, the other physicochemical properties were somewhat the same. The present results suggest the applicability of RiceSorb® for loose face powders.

A Cold Process Preparation of Vetiveria zizanioides (L.) Nash Oil Lotions using Simulgel FL as an Emulsifier.

Vetiveria zizanioides (vetiver) contains viscous volatile oil, which has the ability to repel mosquitoes similar to citronella oil, a well-known mosquito repellent in tropical countries, like Thailand. The objectives of the current study were to formulate the stable oil-in-water vetiver oil lotions using Simulgel FL as a liquid emulsifier, to investigate the physicochemical properties of the prepared lotions and to evaluate the in vitro release characteristics of the stable vetiver oil lotions. In this work, the concentrations of Simulgel FL ranged from 1% to 3% weight in weight, whereas the concentrations of vetiver oil were varied: 2.5%, 5%, and 10% weight in weight. The suitable concentration of Simulgel FL was found to be 3% weight in weight. For comparison purposes, oil-in-water citronella oil lotions (10% weightin- weight citronella oil) were also prepared with similar ingredients. A mixture of vetiver oil and citronella oil (1:1 by weight) was also used as an active ingredient. By using Simulgel FL, the lotions could be prepared using a cold process (without heat). The physicochemical properties (appearance, pH, viscosity) of the stable lotions were satisfactory. All prepared lotions possessed weak acidic pH values with pseudoplastic flows. Using modified Franz diffusion cell and synthetic membrane, the release rates of vetiver oil were relatively lower than those of citronella oil.

Physicochemical properties, in vitro release and skin permeation studies of a topical formulation of standardized pomegranate rind extract.

The aim of the present study was to develop a stable formulation containing standardized pomegranate rind extracts (SPRE) for topical use in the treatment of dermal diseases. Ellagic acid (EA) as the major active constituent of SPRE (not less than 13%) was quantified by HPLC as an indicator for studies on the stability, in vitro drug release, and skin penetration/retention. The formulation prepared with polyethylene glycols (PEG 400 and PEG 4000) containing 5% SPRE has been found to be stable and provide a release rate of 36.6741±5.0072 µg/cm(2)/h that was best fitted to the zero-order kinetic model. EA from SPRE did not penetrate the full-thickness rat skin but the skin retention of EA was determined to be 2.22±0.16 µg/cm(2) with a total recovery of 95.14±5.51%. The results indicated that this 5% SPRE PEG ointment was of satisfactory physicochemical properties and worth further in vivo investigations.

Topical anti-inflammatory potential of standardized pomegranate rind extract and ellagic acid in contact dermatitis.

The present study evaluated the topical anti-inflammatory potential of a standardized pomegranate rind extracts (SPRE) in parallel with its marker compound ellagic acid (EA, 13% w/w) against a mouse model of contact dermatitis. In the phenol-induced mouse ear edema, topical application of SPRE (5, 2.5, and 1 mg/ear) and EA (0.65, 0.325, and 0.13 mg/ear, equivalent to its content in SPRE) dose-dependently reduced the ear edema with the maximal inhibition of 79.12% and 73.63%, respectively. Triamcinolone (0.1 mg/ear) and diclofenac (1 mg/ear) as reference drugs inhibited the edema by 73.63% and 37.91%. Myeloperoxidase (MPO) activity in the mouse ear was also decreased by SPRE and EA up to 69.68% and 68.79%, respectively. Triamcinolone and diclofenac decreased the MPO activity by 76.66% and 80.14% similarly. The results indicated that topical application of SPRE and EA is promising for use in the treatment of inflammatory skin disorders.

Effects of glucam P-20, vanillin, and fixolide on mosquito repellency of citronella oil lotions.

The objective of this study was to investigate the effects of three fragrance fixatives, Glucam P-20, Vanillin, and Fixolide, on the mosquito repellent property of citronella oil lotions. In the current study, two formulae (A and B) of oil-in-water citronella oil lotions were formulated using different ingredients (emulsifiers [Cremophors or Emulwax], stiffening agents, and emollients). Citronella oil was used at 10% wt:wt. The weight ratios tested between citronella oil and each fixative were 1:0.25, 1:0.5, and 1:1. Overall, 20 formulations, including one with no fixatives for both A and B, were produced, A1-A10 and B1-B10. The repellent activities of these 20 lotions against Aedes aegypti (L.) were tested using a human-bait technique. The types and concentrations of fixatives as well as the compositions of the formulations did affect the protection time of the citronella oil lotions. The lotion containing Emulwax and 5% vanillin (B6) was the most effective repellent. It provided the longest protection time of 4.8 h, which exceeded the minimum requirement of 2 h set by the National Institute of Health, Thailand. The shortest protection time (1 h) was observed in the lotion containing Emulwax and 2.5% Glucam P-20 (B2). It could be concluded that the tested fixatives affected the repellent activity of the citronella oil lotions.

Characterization and release kinetics of nicotinamide microemulsion-based gels.

The aim of this study was to investigate physicochemical characteristics and to determine in vitro release kinetics of prepared nicotinamide microemulsion-based gels (MBGs). Nicotinamide microemulsions (ME) were composed of 3% w/w nicotinamide, 7% w/w water, 25% w/w soybean oil, and 65% w/w of 9:1 oleth-10:isopropyl alcohol mixture. A water-in-oil (w/o) type ME was converted to three MBGs. ME was combined with 5% w/w of colloidal silica to obtain MBG-1, with 5% w/w of 0.5% w/w carbomer solution to obtain MBG-2, or with a mixture of 3% w/w of 0.5% w/w carbomer solution and 2% w/w of PEG-40 hydrogenated castor oil to obtain MBG-3. The results indicated that MBG-1 was a clear gel with plastic flow while MBG-2 and MBG-3 were turbid gels with Newtonian flow. MBG-1 was physically and chemically stable at 4°C as well as at ambient temperature (approximately 30°C) during the 2-month study period. The color darkened when stored at 60°C. The release kinetics of MBG-1 was best fitted to zero order model. The in vitro release of nicotinamide from MBG-1 through cellulose membrane was compared with that from the ME and an oil-in-water (o/w) commercial cream (CC). The rank order of release rate of nicotinamide from different formulations was MBG-1 > ME > CC.

Development of a pH-responsive drug delivery system for enantioselective-controlled delivery of racemic drugs.

This study aimed to develop enantioselective-controlled drug delivery systems for selective release of the required (S)-enantiomer in a dose formulation containing a racemic drug in response to pH stimuli. The recognition system was obtained from a nanoparticle-on-microsphere (NOM) molecularly imprinted polymer (MIP) with a multifunctional chiral cinchona anchor synthesised by suspension polymerisation using ethylene glycol dimethacrylate as a cross-linker. (S)-omeprazole was used as an imprinting molecule conferring stereoselectivity upon the polymers. The ability of the prepared recognition polymers to selectively rebind (S)-omeprazole was evident at different pH levels (the highest being at pH 7.4). The partial selective-release phenomenon of the (S)-enantiomer in MIP-containing composite cellulose membranes with increased vehicular racemic omeprazole concentrations was highly pH-dependent. Cinchona-bonded polymers imprinted with (S)-omeprazole could recognise the moldable contact site of (S)-omeprazole independently of its chirality; this is responsible for the delivery of (S)-enantiomer from racemic omeprazole. The controlled-release drug devices were fabricated with synthesised composite latex, and consisted of a pH stimuli-responsive poly(hydroxyethyl methacrylate) (HEMA) and polycaprolactone-triol (PCL-T) blend, and a MIP with preloaded drug, along with pH 7.4 buffer in the device's interior. The results demonstrate that drug delivery systems containing (S)-omeprazole imprinted cinchona-polymer nanoparticle-on-microspheres may maximise efficacy while minimising dose frequency.

Crystal structure transformations and dissolution studies of cimetidine-piroxicam coprecipitates and physical mixtures.

We have recently demonstrated that coprecipitation of cimetidine (C) and piroxicam (P) at a mole ratio of 1:1 results in the transformation of the crystalline forms of both drugs to an amorphous state. In this study, coprecipitates and physical mixtures of cimetidine and piroxicam were further investigated at C/P mole ratios of 1:10, 1:5, 1:4, 1:2, 10:1, 20:1, 30:1, 40:1, and 52.5:1, the latter being the composition of a clinically used dosage. The physicochemical properties of these samples were examined using X-ray diffraction and Fourier transform infrared spectroscopy. Additionally, dissolution of piroxicam in the samples at C/P mole ratios of 10:1, 20:1, 30:1, 40:1, and 52.5:1 was investigated at pH 1.2 and pH 4. In coprecipitates with C/P mole ratios of 10:1, 20:1, 30:1, and 40:1, crystalline forms of both drugs were transformed to amorphous states. A mixture of an amorphous state and cimetidine crystalline form A was observed for the coprecipitate with a C/P mole ratio of 52.5:1. For the coprecipitates with C/P mole ratios of 1:2, 1:4, 1:5, and 1:10, cimetidine form A was transformed to form C, whereas piroxicam form II was modified to form I. It is interesting that small molecules, instead of polymers or solvents, can cause such crystal structure transformations. The dissolution of piroxicam at pH 4 is lower than that at pH 1.2. Additionally, the coprecipitates and physical mixtures with C/P mole ratios of 10:1, 20:1, 30:1, 40:1, and 52.5:1 demonstrate substantially higher dissolution of piroxicam compared to that of drug alone.

Microemulsions and nanoemulsions: novel vehicles for whitening cosmeceuticals.

For Asian women, white skin is preferable. During the last decade, skin whitening products appear to be the largest and continually growing segment in skin-care market in Asia and have an impaction of economic worth. Skin whitening or lightening agents are as cosmetics which act as a drug-like benefit since melanin producing process of the skin is disturbed and can be classified as cosmeceuticals. To increase efficiency, novel vehicles are necessary for skin penetration enhancement of these agents. Microemulsions and nanoemulsions are one of useful nanocarriers for skin application in view of achieving efficiency of the active substances. Moreover, they can be formulated with ease for active ingredient incorporation, high stability and good appearance. In this review article, applications of well-known whitening or lightening agents were summarized. In addition, the use of microemulsions and nanoemulsions as novel vehicles for whitening products were discussed.

S-propranolol imprinted polymer nanoparticle-on-microsphere composite porous cellulose membrane for the enantioselectively controlled delivery of racemic propranolol.

Molecularly imprinted polymer (MIP) nanoparticle-on-microspheres (NOM) selective for S-propranolol were successfully prepared using suspension polymerization involving agitation of the reaction mixture at high speed. The integration of the MIP-NOM into a self-assembled porous cellulose membrane allowed a controlled distribution and availability of the molecule recognition sites within a porous structure. The nature of the membrane-included microparticles determined the degree of porosity whilst the adherent nanoparticles provided an increased surface area enabling the composite membrane to be employed efficiently for the trans-membrane transport of the imprinted molecule. The MIP-NOM within the membrane were easily accessible for binding of the imprinted molecule and appeared to maintain high selectivity, indicating that the composite membranes may potentially provide valuable affinity matrices. In this study, the application for MIP-NOM composite cellulose membranes were investigated for their potential to act as transdermal drug delivery systems for the S-enantiomers from racemic propranolol, its ester prodrugs (cyclopropanoyl- and valeryl-propranolol) or other beta-blockers (pindolol and oxprenolol). The enantioselective release of the fluorescently active 1-pyrene-butyryl ester prodrug of S-propranolol from MIP-NOM composite membranes and its diffusion and transit across excised rat skin was monitored by confocal laser scanning microscopy. The mechanism underlying the release of S-propranolol from the MIP-NOM composite membrane was found to involve specific adsorption and mobility of this enantiomer at the binding site in the MIP-NOM as the latter undergo a transition from the dry to wet state. The proposed MIP-NOM composite membrane controlled release system may be applicable for fabrication of novel membranes with self-controllable permeability responding to the presence of target solutes.

Transdermal delivery of hydrophobic and hydrophilic local anesthetics from o/w and w/o Brij 97-based microemulsions.

PURPOSE: To characterize the physicochemical properties of drug-loaded oil-in-water (o/w) and water-in-oil (w/o) Brij 97-based microemulsions in comparison to their blank counterparts and to investigate the influence of microemulsion type on in vitro skin permeation of model hydrophobic drugs and their hydrophilic salts. METHODS: The microemulsion systems were composed of isopropyl palmitate (IPP), water and a 2:1 w/w mixture of Brij 97 and 1-butanol. The samples were characterized by visual appearance, pH, refractive index, electrical conductivity, viscosity and determination of the state of water and IPP in the formulations using differential scanning calorimetry (DSC). Transdermal flux of lidocaine, tetracaine, dibucaine and their respective hydrochloride salts through heat-separated human epidermis was investigated in vitro using modified Franz diffusion cells. RESULTS: The physicochemical properties of drug-loaded microemulsions and their blank counterparts were generally similar; however, slight changes in some physicochemical properties (apparent pH and conductivity) were observed due to the intrinsic properties of the drugs. The o/w microemulsions resulted in the highest flux of lidocaine, tetracaine and dibucaine as compared to the other formulations with in the same group of drugs. CONCLUSIONS: The characterization results showed that incorporation of the model drugs into the microemulsions did not change the microemulsion type. The permeation data exhibited that the nature of the microemulsions was a crucial parameter for transdermal drug delivery. The o/w microemulsions containing hydrophobic drugs provided the highest skin permeation enhancement. In addition, skin permeation was depended on the molecular weight of the model drugs.