Yew Weng Chan

Terpenes in ethanol: haloperidol permeation and partition through human skin and stratum corneum changes

Carvacrol, linalool and alpha-terpineol (5% w/v) in 50% ethanol were used to enhance the permeation of haloperidol (HP) through human skin in vitro and their enhancement mechanism was investigated with HP-stratum corneum (SC) binding studies, fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Carvacrol followed by terpineol and linalool enhanced flux and permeability coefficient but only carvacrol provided the required plasma concentration and the permeated daily doses. All terpenes increased the activity coefficient of HP in the skin. Carvacrol increased the lag time, which could be due to slow redistribution within SC. The thermogram of hydrated SC showed two lipid endotherms T1 and T2 at 65 and 78 degrees C and protein endotherm T3 at 97 degrees C. All endotherms were absent after SC treated for 48 h with 12 ml of terpene solutions and a decrease in melting points (m.p.) of lipids with a shift of protein endotherm were observed after 12 h treatment with 7 ml of terpene solutions. Linalool and terpineol decreased the m.p. of T1 to 33 degrees C. Carvacrol increased the T1 peak area, which was attributed to lateral lipid bilayer swelling. The IR spectra showed decreases in peak areas and heights of CH2 stretchings but did not show shift of these peaks, increase in their peak widths and shift in amide bands. All the three terpenes disrupted the lipid bilayer and extracted the lipids. Moreover, carvacrol increased the partition of HP whilst linalool and terpineol fluidized the lipids at skin temperature. There could be other possible protein-terpene interactions.

Novel Vitamin and Gold-Loaded Nanofiber Facial Mask for Topical Delivery

Abstractl-ascorbic acid has been widely used in cosmetic and dermatological products because of its ability to scavenge free radicals and destroy oxidizing agents. However, it is chemically unstable and can easily be oxidized. The current cosmetic facial masks available in the market are pre-moistened, which means that the aqueous fluid content of the mask may oxidize some of the unstable active ingredients such as ascorbic acid. This work presents an anti-wrinkle nanofiber face mask containing ascorbic acid, retinoic acid, gold nanoparticles, and collagen. This novel face mask will only be wetted when applied to the skin, thus enhancing product stability. Once moistened, the content of the mask will gradually dissolve and release the active ingredients and ensure maximum skin penetration. The high surface area-to-volume ratio of the nanofiber mask will ensure maximum contact with the skin surface and help to enhance the skin permeation to restore its healthy appearance. Electrospun fiber mats may provide an attractive alternative to the commercial facial cotton masks.

Smart Polymeric Nanofibers for Topical Delivery of Levothyroxine

Topical administration of levothyroxine (T₄) helps to reduces deposits of adipose tissue on skin. The question is whether topical application of T₄ could lead to systemic effects. In the present study a series of nanofibrous membranes were electrospun into blends of poly vinyl alcohol (PVA) and poly-N-isopropylacrylamide (PNIPAM) to develop a sustained topical delivery of T₄. The polymeric nanofiber mats were characterized by field emission scanning electron microscopy (FESEM) and fourier transform infrared (FTIR) spectroscopy. In vitro permeation of the drug from the polymeric nanofibers was studied using excised human skin and the permeation mechanism investigated using confocal microscopy. It was observed that polymeric nanofibers were able to sustain the penetration of T₄ to the skin and help maintain the effective drug concentration in the skin layers for longer period of time. These formulations may have potential uses in topical skin products and can help to increase the accumulation of the active compound on the skin surface thus minimize the adverse side effects which may be caused by systemic absorption. This may result in great improvement in consumer compliance, avoid frequent dosing and enhance the therapeutic effectiveness.

Alkalinization of lidocaine does not hasten the onset of axillary brachial plexus block.

We assessed the onset of sensory and motor blockade as well as the distribution of sensory blockade after axillary brachial plexus block with 1.5% lidocaine hydrochloride 1:200,000 epinephrine with and without sodium bicarbonate in 38 patients. The onset of analgesia and anesthesia was recorded over the distributions of the median, ulnar, radial, and medial cutaneous nerves of the forearm, medial cutaneous and lateral cutaneous nerves of the arm, and musculocutaneous nerve. The onset of motor blockade of elbow and wrist movements was also recorded. Data were analyzed by using survival techniques and compared by using log rank tests. Only the onset of analgesia in the medial cutaneous nerves of the arm and forearm, and the onset of anesthesia in the medial cutaneous nerve of the arm were significantly faster (P < 0.05) with alkalinization of lidocaine. Our study showed that alkalinization of lidocaine does not significantly hasten block onset in most terminal nerve distributions. Implications: We examined whether alkalinizing a local anesthetic would quicken the onset of a regional upper limb nerve blockade. We found that alkalinization of lidocaine did not offer a significant clinical advantage in axillary brachial plexus blockade. (Anesth Analg 1998;86:566-8)

Surface tension and wettability in transdermal delivery: a study on the in‐vitro permeation of haloperidol with cyclodextrin across human epidermis

Objectives The aim of this work was to study the effect of surface tension and contact angle on the permeation of haloperidol across human skin using cyclodextrin derivatives.OBJECTIVES This work evaluated the potential usefulness of pharmacological activation of cardiac ATP-sensitive potassium channels (K(ATP)) in the prevention of drug-induced QT prolongation in anaesthetised guinea-pigs. Prolongation of cardiac repolarisation and QT interval is an adverse effect of many drugs blocking HERG potassium channels. This alteration can be dangerously arrhythmogenic and has been associated with the development of a particular form of ventricular tachyarrhythmia known as torsade de pointes. METHODS The well-known K(ATP) openers aprikalim, cromakalim and pinacidil were used. Moreover, three benzothiazine derivatives, which have been reported as potent activators of K(ATP) channels, were also used. KEY FINDINGS Pharmacological activation of K(ATP) channels caused a reduction of the QT prolongation, induced by astemizole, cisapride, quinidine and thioridazine. In contrast, the QT prolongation induced by haloperidol, sotalol and terfenadine, which are known to block HERG channels but also K(ATP) channels, was not influenced by K(ATP) activation. Glibenclamide and tolbutamide (non-selective blockers of K(ATP) channels expressed both in sarcolemmal and in mitochondrial membranes) antagonised the effects of K(ATP) openers, whereas 5-hydroxydecanoic acid (selective blocker of the mitochondrial K(ATP) channels) failed to antagonise the effects of K(ATP) openers, indicating that only the sarcolemmal K(ATP) is involved in the cardioprotective activity. CONCLUSIONS The data suggest that pharmacological K(ATP) activation might represent an option for treatment of patients exposed to QT-prolonging drugs.

Development and characterization of skin permeation retardants and enhancers: A comparative study of levothyroxine-loaded PNIPAM, PLA, PLGA and EC microparticles

Polymeric microparticles suitable for topical and transdermal delivery systems were studied using poly d,l lactide (PLA), poly d,l lactide co glycoside (PLGA), poly (N‐isopropylacrylamide) (PNIPAM) and ethyl cellulose (EC). Drug encapsulation efficacy, microparticle stability and skin permeation studies of levothyroxine loaded microparticles were carried out using excised human skin, and the skin permeation pattern was observed using confocal laser scanning microscopy.

Lipid vesicles for the skin delivery of diclofenac: Cerosomes vs. other lipid suspensions

PURPOSE Lipid suspensions as drug carriers, including conventional liposomes, ethosomes, transferosomes, proniosomes, niosomes, PEG-PPG-PEG niosomes and stratum corneum liposomes (cerosomes), were formulated and compared. METHODS Lipid vesicles were formulated and assessed with regards to enhancement of skin permeation of diclofenac and stability profiles of the formulations. Formulation-induced changes of the biophysical structure of excised human skin were monitored using the Fourier transform infrared spectroscopy. RESULTS The stability profiles of these suspensions over 12 weeks did not show any significant drug leakage from the vesicles of interest (p > 0.05). FTIR observations indicated that the vesicles increased stratum corneum (SC) lipid fluidization and altered protein conformation. Skin permeability experiments showed that the free unencapsulated drug in the cerosomal formulations caused significant increase in drug permeation across the skin (p < 0.01). Low skin permeability of drug from the other lipid suspensions could be due to the entrapment of diclofenac within these vesicles which decreased the solubility of the hydrophilic drug in the skin lipids and the partition coefficient of the drug from these vesicles into the SC. CONCLUSION Optimal drug entrapment in vesicles or alteration of the skin structure may not necessarily enhance the permeation of hydrophilic drugs across the human skin. These lipid vesicles may be further developed into carriers of both hydrophilic and hydrophobic drugs for topical and transdermal delivery, respectively.

Ascorbic Acid for the Safe Use of a Sunscreen Agent: Accumulation of Nano Zinc Oxide and Titanium Dioxide on the Skin

Objective Physical UV absorbers such as titanium dioxide or zinc oxide have been found to be highly protective against ultraviolet radiation. Sun protection factor depends on the accumulation of the minerals on the skin. UV-absorbing agents must accumulate within the upper skin layers in order to provide a dense light-absorbing layer and guarantee water resistance. The aim of this work was to increase the skin deposition and efficacy of sunscreens without increasing their skin permeation. The application possibility of EDX to determine the quantitative elemental composition of zinc and titanium on the skin surface was studied. Method The changes induced in the skin deposition of physical UV absorbers in conjunction with ascorbic acid were studied. In vitro skin permeation and X-ray elemental analysis were carried out to determine the mineral skin deposition effect of ascorbic acid. Key findings Results indicate that ascorbic acid may significantly increase the skin deposition (p < 0.05) of these minerals on the skin without increasing their skin permeation (p > 0.05). Flow through diffusion cell and X-ray elemental analyses appear to be complementary and show that ascorbic acid is able to increase accumulation of sunscreen on the skin.