Sung-Chang Chung

Targeted and sustained delivery of hydrocortisone to normal and stratum corneum-removed skin without enhanced skin absorption using a liposome gel

A liposome-gel formulation containing 1% (w/w) hydrocortisone was prepared by blending phosphatidylcholine liposomes of hydrocortisone with Carbopol 934 hydrogel. The liposome-gel was applied topically onto the normal and stratum corneum (SC)-removed skins (3.0 cm2) of hairless mice at a dose of 1 mg as hydrocortisone. Percutaneous absorption of hydrocortisone across the SC-removed skin was significantly faster than that across normal skin, suggesting that SC behaves as a penetration barrier for the liposome-bound drugs. Contrary to previous reports that have suggested enhanced percutaneous penetration of drugs by liposomes, the liposome-gel in this study reduced the skin absorption of hydrocortisone, compared with the conventional ointment formulation. The amount of hydrocortisone absorbed from the liposome-gel after 8 h into the SC-removed skin was less than one-third of that from the conventional ointment. In spite of the reduced absorption, higher and sustained skin concentrations of hydrocortisone were achieved for the liposome-gel as compared to the ointment. Drug concentration in both viable and deep skin reached its maximum within 0.5 h after application of both formulations to both skin types. Drug concentrations in both skins from the ointment declined as a function of time, while those from the liposome-gel were greatly sustained. The sustainment by the liposome-gel was more remarkable in the viable skin than in the deep skin. Drug concentration in the viable skin could be maintained at a nearly constant level for over 8 h by applying the liposome-gel. As a result, a 5-fold higher viable skin drug concentration was obtained from the liposome-gel than from the ointment at 8 h after the application to the SC-removed skin. Nevertheless, the plasma concentration of hydrocortisone at 4 h from the liposome-gel was only one-fourth (p<0.01) the value from the ointment when the drug was applied to the SC-removed skin. Thus, retarded diffusion of the drug from the skin to the systemic blood stream appears to be a potential factor in the sustained skin concentration of hydrocortisone from the liposome-gel. The retarded diffusion was supported by the lower urinary (one-third, p<0.05) and fecal (one-half, p<0.05) excretion of the drug from the liposome-gel as compared to the ointment when the drug was applied to SC-removed skin. Interaction of hydrocortisone in the skin with phosphatidylcholine, a component of the liposomes and skin, may well be a factor in retarding the diffusion of the drug in the skin.

Delivery of ofloxacin to the lung and alveolar macrophages via hyaluronan microspheres for the treatment of tuberculosis.

Microspheres containing ofloxacin (HMO) with a mean diameter of 2-5 mum were prepared by the co-spray drying of ofloxacin and the sodium salt of hyaluronic acid (hyaluronan). Recovery of lactose blends of HMO from stage II of the twin-stage impinger (TSI) reached 43%, indicating favorable delivery of the drug to the lung via inhalation. The area under the ofloxacin concentration curve from time zero to infinity (AUC) was estimated for plasma and lungs in rats following intratracheal (it), intravenous (iv), and oral (po) administration of HMO, ofloxacin microspheres (MO), and an aqueous solution of ofloxacin (OS), at an equivalent ofloxacin dose of 8 mg/kg rat. The AUC ratio between the lung and plasma for it-administered HMO was.10.9-, 9.3- and 1.8-fold greater than iv OS, po OS, and it MO, respectively, suggesting that the most efficient delivery of ofloxacin to the lung is feasible via HMO. Moreover, in vitro uptake of ofloxacin from HMO by air-surface cultured alveolar macrophages (RAW 264.7) was 2.1- and 1.7-fold higher than ofloxacin uptake from OS and MO (P<0.05). Taken together, the results of the present study demonstrate that pulmonary administration of ofloxacin via HMO would improve the treatment efficacy of ofloxacin against tuberculosis, compared to other forms of ofloxacin (OS and MO) and to other routes of administration (iv and po).

Evaluation of Pressure Pain Threshold in Head and Neck Muscles by Electronic Algometer: Intrarater and Interrater Reliability

Using a new electronic algometer, the mean values and standard deviations of pressure pain threshold and the intrarater and interrater reliability were evaluated on 13 muscles of the human head and neck region. The subjects were 40 healthy individuals, 21 females and 19 males. A comparison with data obtained from contralateral muscles failed to demonstrate significant differences. Statistically significant correlation coefficients were obtained from the values of intra-examiners and inter-examiners in all muscles except the medial pterygoid and middle sternocleidomastoid muscle in male subjects (p < 0.05). This study showed that the electronic algometer could be recommended for evaluation of the pressure pain threshold of human head and neck muscles in clinical and experimental studies.

Accelerated oral absorption of gliclazide in human subjects from a soft gelatin capsule containing a PEG 400 suspension of gliclazide

Whether a rapid elevation of serum gliclazide concentration in human subjects can be achieved through an acceleration of dissolution of gliclazide from a formulation was examined. A soft gelatin capsule containing PEG 400, PEG 4000, Tween 20 and glycerin was prepared as a formulation that may accelerate dissolution of gliclazide. The in vitro dissolution of gliclazide at pH 7.2 was identical for the soft capsule and conventional tablets, Diamicron and Diberin. However, at pH 1, 2 and 4.0 the dissolution from the soft capsule was more rapid compared to the tablets. When bioavailability parameters were compared following oral administration of the soft capsule and Diamicron to 16 healthy Korean male subjects, the parameters representing the amount of adsorption (i.e. the area under the serum gliclazide concentration vs. time curve up to 24 h, AUC24, and the peak serum concentration Cmax) were not statistically different for both formulations. However, the time required to reach the peak (Tmax) was significantly shorter for the soft capsule than for the Diamicron. Our results, therefore, indicate that a rapid elevation of serum gliclazide concentration following oral administration of a formulation can be achieved by accelerating the in vitro dissolution of gliclazide from the formulation into the acidic buffers. Thus, the rate of gastrointestinal absorption of gliclazide appears to be dependent on its in vivo dissolution rate in gastric fluid. A soft capsule containing a PEG 400 suspension of gliclazide appears to be an appropriate formulation for accelerating the dissolution.

Volatile sulfur compounds produced by Helicobacter pylori.

Goals To assess the volatile sulfur compounds produced by three strains of Helicobacter pylori in broth cultures mixed with sulfur-containing amino acids. Background Halitosis has been reported in H. pylori–positive patients, and volatile sulfur compounds such as hydrogen sulfide and methyl mercaptan are known to be responsible for inducing oral malodor. Whether H. pylori produces these volatile sulfur compounds has yet to be established. Study Three strains of H. pylori (ATCC 43504, SS 1, DSM 4867) were cultured with 5 mM cysteine and methionine. After 72 hours of incubation, the headspace air was aspirated and injected directly into a gas chromatograph. The concentrations of hydrogen sulfide and methyl mercaptan were analyzed and compared between experimental and control cultures Results In broth containing 5 mM cysteine, hydrogen sulfide was increased by ATCC 43504 (P<0.01) and SS 1 (P<0.05), while methyl mercaptan was elevated only by SS 1 (P<0.05). In broth containing 5 mM methionine, methyl mercaptan increases were significant for SS 1 (P<0.05) and DSM 4867 (P<0.05). In broth containing 5 mM cysteine and 5 mM methionine, the concentration of hydrogen sulfide was higher than in controls for all three strains (P<0.01); that of methyl mercaptan was higher only for SS 1 (P<0.01). Cysteine addition to cultures containing methionine increased hydrogen sulfide and methyl mercaptan for ATCC 43504 (P<0.05) and SS 1 (P<0.05). Conversely, addition of methionine to cultures containing cysteine increased methyl mercaptan only for DSM 4867 (P<0.01). Conclusions The production of volatile sulfur compounds by H. pylori is not only very complicated but also strain-specific. Nevertheless, H. pylori was shown to produce hydrogen sulfide and methyl mercaptan, which suggests that this microorganism can contribute to the development of halitosis.

The Effect of the Stabilization Splint on the TMJ Closed Lock

The mandibular manipulation technique and anterior repositioning splint are considered acceptable conservative therapies for an acute temporomandibular joint (TMJ) closed lock. However, an anterior repositioning splint will result in a corresponding change in occlusion, such as posterior open-bite. Furthermore, invasive treatments such as surgery have many complications. This article describes the effect of the stabilization splint with more conservative therapies, including the manipulation technique, wherein the complications are minimal. In this study, the authors used the stabilization splint instead of the anterior repositioning splint. They obtained acceptable results, including the increase of interincisal distance, a decrease in Frictons craniomandibular index, and a decrease in Helkimos clinical dysfunction index. Therefore, the treatment method that is composed of a stabilization splint, manipulation, moist heat, and exercise should be considered as the first choice of treatment for TMJ closed lock, as opposed to a repositioning splint.

Prevalence and patterns of nocturnal bruxofacets on stabilization splints in temporomandibular disorder patients.

ABSTRACT The purpose of this study was to investigate the prevalence of nocturnal bruxism, the characteristics of bruxofacets, and the reduction of symptoms in temporomandibular disorder (TMD) patients. The study involved the observation of bruxofacets on a stabilization splint. Twenty-six patients (22 women and 4 men, 16–54 years of age) with signs and symptoms of TMD were given an initial examination before using a splint, and then at intervals of one, three, six and ten weeks after a stabilization splint was first used. In 88% of the patients (n=23) active shiny facets or scratches caused by nocturnal bruxism appeared on the occlusal surface of splints within ten weeks. In 52% of the 23 patients these facets were created by bilateral mandibular excursions, in 35% by small lateral movements, and in 13% by unilateral excursions. Subjective pain and the Craniomandibular Index in patients had decreased after ten weeks (p<0.001), but a reduction of symptoms did not differ according to the patterns of the bruxofacets. It was concluded that most TMD patients have a parafunctional habit, namely bruxism. Further research is needed to produce more convincing evidence of a true cause-and-effect relationship between nocturnal bruxism and TMD.

Reliability and Validity of the Pressure Pain Thresholds (PPT) in the TMJ Capsules by Electronic Algometer

Pressure pain thresholds (PPT) of 39 normal subjects (20 males and 19 females) and 30 female patients with temporomandibular joint (TMJ) capsulitis (21 lateral and 25 posterior capsulitis) were examined by an electronic algometer. In normal subjects, statistically significant correlation coefficients were obtained from the values of intra-examiners and inter-examiners in both lateral and posterior TMJ capsules (p < 0.01). A comparison with data obtained from contralateral sides failed to demonstrate significant differences. Statistically significant differences were found between the PPT of normal female subjects and female patients with capsulitis in both lateral and posterior TMJ capsules (p < 0.01).