Cerebrolysin Amelioration of Spinal Cord Ischemia/ Reperfusion Injury in Rabbit Model.

AIM: To investigate the effects of cerebrolysin on inflammation, oxidative stress, apoptosis, and neurologic recovery in the setting of an experimental rabbit model of spinal cord ischemia/reperfusion injury (SCIRI). MATERIAL AND METHODS: Rabbits were randomly divided into five groups: control, ischemia, vehicle, methylprednisolone (30 mg/kg), and cerebrolysin (5 ml/kg) group. The rabbits in the control group underwent only laparotomy; the other groups underwent spinal cord ischemia and reperfusion injury for 20 minutes. Neurologic examination after 24 hours was based on the Modified Tarlov scale. Myeloperoxidase activities, catalase and malondialdehyde levels, and caspase-3 concentrations were determined in serum and tissue samples. Serum xanthine oxidase levels were studied and histopathological and ultrastructural changes were examined. RESULTS: After SCIRI, serum and tissue myeloperoxidase activities, malondialdehyde levels, caspase-3 concentrations, and serum xanthine oxidase activities were increased (p < 0.01?0.001). Catalase levels were significantly diminished (p < 0.001). Cerebrolysin treatment correlated with reduced myeloperoxidase and xanthine oxidase activities, malondialdehyde levels and caspase-3 concentrations; and with increased catalase levels (p < 0.001, for all). The cerebrolysin group showed improved histopathological, ultrastructural, and neurological outcomes. CONCLUSION: For the first time in the literature, the current study reports anti-inflammatory, antioxidant, antiapoptotic, and neuroprotective effects of cerebrolysin in a SCIRI rabbit model.

URTICA DIOICA EXTRACT DOWNREGULATES THE GENE EXPRESSION OF 5Α-RII IN HACAT CELLS: POSSIBLE IMPLICATIONS AGAINST ANDROGENIC SKIN DISEASES.

Urtica dioica (Ud) is a perennial plant of temperate climate regions and has been reported therapeutic activity against benign prostate hyperplasia, mainly due to its 5-alpha-reductase (5α-R) inhibition feature, which has been singly shown only in prostatic tissues until now. Also considering its use in traditional medicine against some dermatological problems and hair loss, we performed an in-vitro study to reveal its 5α-R inhibition activity in skin cells whether this plant may have a therapeutic potential against androgenic skin diseases. After the preparation of Ud leaf extract and determination of non-cytotoxic concentration, cultured HaCaT cells were treated with the plant extract. RNA isolations were carried out from both non-treated and treated cell groups. cDNA synthesis was performed using gene specific primers of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as reference gene and 5α-R type II (5α-RII) as study material. Gene expressions were determined by real time reverse transcription quantitative polymerase chain reaction analysis. Results were represented as 'Target/GAPDH Fold Change'. Results of gene expression analysis showed that plant extract caused statistically significant downregulation of 5α-RII gene expression (p=0.0021) in treated cells, compared to untreated control cells, and ended up with 0.5873±0.0586 fold change. This study is the first one showing the suppression of 5α-RII gene expression on skin cells with unmixed or solitary Ud extract. With the currently reported anti-androgenic activity in HaCaT cells, it can be suggested that Ud has a solid scientific base and may have a promising future in cosmetic dermatology, and new product development against androgenic skin diseases.

Neuroprotective Effects of Dexpanthenol on Rabbit Spinal Cord Ischemia/Reperfusion Injury Model.

OBJECTIVE: Dexpanthenol (DXP) reportedly protects tissues against oxidative damage in various inflammation models. This study aimed to evaluate its effects on oxidative stress, inflammation, apoptosis, and neurological recovery in an experimental rabbit spinal cord ischemia/reperfusion injury (SCIRI) model. METHODS: Rabbits were randomized into 5 groups of 8 animals each: group 1 (control), group 2 (ischemia), group 3 (vehicle), group 4 (methylprednisolone, 30 mg/kg), and group 5 (DXP, 500 mg/kg). The control group underwent laparotomy only, whereas other groups were subjected to spinal cord ischemia by aortic occlusion (just caudal to the 2 renal arteries) for 20 min. After 24 h, a modified Tarlov scale was employed to record neurological examination results. Malondialdehyde and caspase-3 levels and catalase and myeloperoxidase activities were analyzed in tissue and serum samples. Xanthine oxidase activity was measured in the serum. Histopathological and ultrastructural evaluations were also performed in the spinal cord. RESULTS: After SCIRI, serum and tissue malondialdehyde and caspase-3 levels and myeloperoxidase and serum xanthine oxidase activities were increased (P < 0.05-0.001). However, serum and tissue catalase activity decreased significantly (P < 0.001). DXP treatment was associated with lower malondialdehyde and caspase-3 levels and reduced myeloperoxidase and xanthine oxidase activities but increased catalase activity (P < 0.05-0.001). Furthermore, DXP was associated with better histopathological, ultrastructural, and neurological outcome scores. CONCLUSIONS: This study was the first to evaluate antioxidant, anti-inflammatory, antiapoptotic, and neuroprotective effects of DXP on SCIRI. Further experimental and clinical investigations are warranted to confirm that DXP can be administered to treat SCIRI.

Surgical outcome of laminoplasty for cervical spondylotic myelopathy: a single-institution experience

Background/aim: Cervical spondylotic myelopathy (CSM) develops as a result of compression of the spinal cord in the cervical region. Early diagnosis and surgical treatment can limit the progression of symptoms. Various surgical approaches and strategies have been described in the literature. This study aims to evaluate the clinical and radiological results of open-door laminoplasty for the treatment of CSM. Materials and methods: In this study, we retrospectively analyzed the patients who underwent expansive open-door laminoplasty secured with titanium miniplates. Thirty-four patients with CSM who were followed up postoperatively for more than 12 months were included in the study. The modified Japanese Orthopaedic Association (mJOA) score was used to assess the degree of myelopathy. We evaluated cervical sagittal alignment with C2­C7 Cobb angle, the ambulatory status with the Nurick grade, and measured postoperative neck pain with the visual analogue scale (VAS). Results: Themeanm JOA score was 11 (range 6­15) preoperatively, and 13.5 (range 9­16) postoperatively with an average 55% recovery rate (range 0­75) (p < 0.001). Themean­Nurick grade was 2 (range 1­3) preoperatively and 1 (range 0­3) postoperatively (p < 0.001). The median cervical lordotic angle increased from 7.5 ° preoperatively to 12.5 ° postoperatively (p = 0.044). K-line (+) patients> mean mJOA scores significantly increased from 10.8 ± 1.7 to 13.3 ± 1.7 postoperatively (p < 0.001). The mean preoperative VAS reduced from 2.66 ± 1.4 to 1.59 ± 1.4 postoperatively (p < 0.001). Conclusion: Open-door laminoplasty technique is an effective surgical procedure that can be used safely to treat cervical spondylotic myelopathy. Our findings suggest that it can limit the progression of symptoms and alter the poor prognosis in CSM.

COVID-19 Detection System Using Chest CT Images and Multiple Kernels-Extreme Learning Machine Based on Deep Neural Network.

OBJECTIVES: Coronavirus disease is a fatal epidemic that has originated in Wuhan, China in December 2019. This disease is diagnosed using radiological images taken with the help of basic scanning methods besides the test kits for Reverse Transcription Polymerase Chain Reaction (RT-PCR). Automatic analysis of chest Computed Tomography (CT) images that are based on image processing technology plays an important role in combating this infectious disease. MATERIAL AND METHODS: In this paper, a new Multiple Kernels-ELM-based Deep Neural Network (MKs-ELM-DNN) method is proposed for the detection of novel coronavirus disease - also known as COVID-19, through chest CT scanning images. In the model proposed, deep features are extracted from CT scan images using a Convolutional Neural Network (CNN). For this purpose, pre-trained CNN-based DenseNet201 architecture, which is based on the transfer learning approach is used. Extreme Learning Machine (ELM) classifier based on different activation methods is used to calculate the architecture's performance. Lastly, the final class label is determined using the majority voting method for prediction of the results obtained from each architecture based on ReLU-ELM, PReLU-ELM, and TanhReLU-ELM. RESULTS: In experimental works, a public dataset containing COVID-19 and Non-COVID-19 classes was used to verify the validity of the MKs-ELM-DNN model proposed. According to the results obtained, the accuracy score was obtained as 98.36% using the MKs-ELM-DNN model. The results have demonstrated that, when compared, the MKs-ELM-DNN model proposed is proven to be more successful than the state-of-the-art algorithms and previous studies. CONCLUSION: This study shows that the proposed Multiple Kernels-ELM-based Deep Neural Network model can effectively contribute to the identification of COVID-19 disease.

The impact of frailty on noninvasive mechanical ventilation in elderly medical intensive care unit patients.

AIM: Many factors affecting noninvasive ventilation (NIV) in critically ill patients have been reported in the literature, but there is no study about the effect of frailty. With this study, the frailty prevalence was evaluated with two different frailty scores among the NIV population of a medical intensive care unit (ICU). Besides, the impact of frailty on NIV success and mortality and its association with NIV application problems were evaluated. METHOD: A prospective observational cohort study was performed on patients who were over 50 years of age and assigned to NIV due to hypercapnic respiratory failure. For the assessment of frailty, Clinical Frailty Scale (CFS) and The Edmonton Frailty Scale (EFS) were used and the ones with CFS ≥5 and EFS ≥8 were considered as fragile. The study population was classified and compared according to NIV success, ICU outcome (discharge or exitus) and NIV application problems. RESULTS: A total of 103 patients with the mean age of 73 ± 11 years were included. The incidence of frailty was 41% with CFS ≥5 and 36% with EFS ≥8. The NIV failure occurred in 30 (29%) patients. Among them frailty and SOFA score was higher; Glasgow Coma Scale (GCS) was lower. In multivariate analysis GCS (OR: 1.2, p: 0.042) and frailty with EFS (OR: 2.8, p: 0.027) were identified as independent risk factors of NIV failure. Sixty-five (63%) patients had NIV application problems and frailty was higher among them with both CFS and EFS (p < 0.05). Mortality occurred in 18 (17%) patients; NIV failure and frailty according to CFS were independent risk factors of mortality. CONCLUSION: The frailty is associated with higher NIV application problems, failure and mortality risk in elderly ICU patients. The CFS and EFS frailty scores can be used to predict NIV success and outcomes in ICUs.

Comparison of the Efficacy of Colistin Monotherapy and Colistin Combination Therapies in the Treatment of Nosocomial Pneumonia and Ventilator-Associated Pneumonia Caused by Acinetobacter baumannii

Objective. To investigate whether there was a difference in mortality; clinical response and bacterial eradication between colistin monotherapy and colistin combination therapies for the treatment of nosocomial pneumonia/ventilator-associated pneumonia (VAP) caused by Acinetobacter baumannii in a medical intensive care unit (ICU).Methods. This retrospective; observational and single-centre study included all patients who were in the medical ICU of Gazi University Medical Faculty Hospital and diagnosed with nosocomial pneumonia/VAP caused by A. baumannii between January 2009 and September 2014. Results. The median age of the 134 patients was 68 years and 53.3% were male. The most common causes of admission were respiratory insufficiency (66.7%) and sepsis/septic shock (54.8%). In patients with nosocomial pneumonia/VAP caused by A. baumannii; on median day 5 of admission; colistin monotherapy was used in 23 (21.6%) patients; a carbapenem combination was used in 80 (59.7%) patients; sulbactam-ampicillin combination was used in 42 (31.4%) patients; tigecycline combination was used in 26 (19.4%) patients; and sulbactam-cefoperazone combination was used in 17 (12.7%) patients. Median ICU stay of the patients was 15.5 days; and 112 (83.6%) patients died. Colistin monotherapy and combination therapies had no superiority over each other in clinical response for the treatment of A. baumannii-associated nosocomial pneumonia/VAP. Mortality was found to be higher in patients receiving the colistin-carbapenem combination (64.3% v. 36.4%; p=0.016). Discharge/day-of-death Sequential Organ Failure Assessment score (odds ratio (OR) 2.017; 95% confidence interval (CI) 1.330 - 3.061) and vasopressor use (OR 9.014; 95% CI 1.360 - 59.464) were independent risk factors for ICU mortality. Conclusion. Colistin monotherapy and combination therapies have no superiority over each other for clinical response in the treatment of nosocomial pneumonia/VAP caused by multidrug-resistant A. baumannii. Colistin-SAM was associated with improved microbiological eradication and colistin-carbapenem combination was associated with increased mortality

Imaging of acute pancreatitis and its complications. Part 1: acute pancreatitis.

Acute pancreatitis is an acute inflammatory disease of the pancreas that may also involve surrounding tissues or remote organs. The Atlanta classification of acute pancreatitis was introduced in 1992 and divides patients into mild and severe groups based on clinical and biochemical criteria. Recently, the terminology and classification scheme proposed at the initial Atlanta Symposium have been reviewed and a new consensus statement has been proposed by the Acute Pancreatitis Classification Working Group. Generally, imaging is recommended to confirm the clinical diagnosis, investigate the etiology, and grade the extend and severity of the acute pancreatitis. Ultrasound is the first-line imaging modality in most centers for the confirmation of the diagnosis of acute pancreatitis and the ruling out of other causes of acute abdomen, but it has limitations in the acute clinical setting. Computed tomography not only establishes the diagnosis of acute pancreatitis, but also enables to stage severity of the disease. Magnetic resonance imaging has earned an ever more important role in the diagnosis of acute pancreatitis. It is especially useful for imaging of patients with iodine allergies, characterizing collections and assessment of an abnormal or disconnected pancreatic duct. The purpose of this review article is to present an overview of the acute pancreatitis, clarify confusing terminology, underline the role of ultrasound, computed tomography and magnetic resonance imaging according to the proper clinical context and compare the advantages and limitations of each modality.

Imaging of acute pancreatitis and its complications. Part 2: complications of acute pancreatitis.

The Atlanta classification of acute pancreatitis was introduced in 1992 and divides patients into mild and severe groups based on clinical and biochemical criteria. Recently, the terminology and classification scheme proposed at the initial Atlanta Symposium have been reviewed and a new consensus statement has been proposed by the Acute Pancreatitis Classification Working Group. Major changes include subdividing acute fluid collections into "acute peripancreatic fluid collection" and "acute post-necrotic pancreatic/peripancreatic fluid collection (acute necrotic collection)" based on the presence of necrotic debris. Delayed fluid collections have been similarly subdivided into "pseudocyst" and "walled of pancreatic necrosis". Appropriate use of the new terms describing the fluid collections is important for management decision-making in patients with acute pancreatitis. The purpose of this review article is to present an overview of complications of the acute pancreatitis with emphasis on their prognostic significance and impact on clinical management and to clarify confusing terminology for pancreatic fluid collections.

Effects of lubricants on binary direct compression mixtures.

The objective of this study was to investigate the effects of conventional lubricants including a new candidate lubricant on binary direct compression mixtures. Magnesium stearate (MGST), stearic acid (STAC), glyceryl behenate (COMP) and hexagonal boron nitride (HBN) were tested. The binary mixtures were 1:1 combinations of spray dried lactose (FlowLac 100), dicalcium phosphate dihydrate (Emcompress), and modified starch (Starch 1500) with microcrystalline cellulose (Avicel PH 102). Tablets were manufactured on a single-station instrumented tablet press with and without lubricants. In the case of unlubricated granules, the modified starch-microcrystalline cellulose mixture provided the highest percent compressibility value at 8.25%, spray dried lactose-microcrystalline cellulose mixture was 7.33%, and the dialcium phosphate dihydrate-microcrystalline cellulose mixture was 5.79%. Their corresponding tablet crushing strength values were: 104 N, 117 N, and 61 N, respectively. The lubricant concentrations studied were 0.5, 1, 2, and 4%. Effects of lubricant type and lubricant concentration on crushing strength were analyzed using a factorial ANOVA model. It was found that the Avicel PH 102-Starch 1500 mixture showed the highest lubricant sensitivity (110 N vs. 9 N), the least affected formulation was FlowLac-Avicel PH 102 mixture (118 N vs. 62 N). The crushing strength vs. concentration curve for MGST showed a typical biphasic profile, a fast drop up to 1% and a slower decline between 1 and 4%. The STAC, COMP, and HBN for all formulations showed a shallow linear decline of tablet crushing strength with increasing lubricant concentration. The HBN was as effective as MGST as a lubricant, and did not show a significant negative effect on the crushing strength of the tablets. The COMP and STAC also did not interfere with the crushing strength, however, they were not as effective lubricants as MGST or HBN.

In vivo evaluation of black and green tea dermal products against UV radiation.

Aqueous extracts of black and green tea (Camellia sinensis) were obtained by freeze-drying for this study. The extracts were evaluated based on tea quality control tests, UV, IR scans, and in vitro antioxidant capacity tests. Dermal products from the tea extracts were designed and manufactured. Black and green tea gels were tested in vivo in the forearms of six subjects using an artifical UV (200-400 nm) source. The tested formulations were green tea gel, black tea gel, 0.3% caffeine gel, carbomer gel base, and a control. Depending on tea quality, the samples resulted in water soluble fractions of 24.5-39.5%. UV and IR scans specifically showed peaks for alkaloids like caffeine, catechins such as epigallocatechin gallate, and polyphenols with dimeric and polymeric structures such as theaflavins (TFs) and thearubigins (TRs). Antioxidant and free radical scavenging activities of black and green tea samples were found to be high and comparable; activity levels for black tea, green tea, high quality black tea, and L-ascorbic acid were 0.48, 0.50, 0.82, and 1.32 mM TR/mg, respectively. No UV-induced erythema was observed at the black and green tea gel sites in any of the subjects. UV-induced erythema was consistently present in various grades at caffeine gel, carbomer gel, and control sites. Results led to the conclusion that freeze-dried black and green tea extracts had strong UV absorbance. Formulating those extracts into dermal gels protected the skin against UV-induced erythema. Therefore, tea extracts were found to be promising candidates for their ability to protect against the harmful effects of UV radiation, such as erythema and premature aging of the skin.

Scintigraphic evaluation of colon targeting pectin-HPMC tablets in healthy volunteers.

The in vivo evaluation of colon-targeting tablets was conducted in six healthy male volunteers. A pectin-hydroxypropyl methylcellulose coating was compressed onto core tablets labelled with 4MBq (99m)Tc-DTPA. The tablets released in the colon in all subjects; three in the ascending colon (AC) and three in the transverse colon (TC). Tablets that released in the TC had reached the AC before or just after food (Group A). The other three tablets released immediately upon AC entry at least 1.5h post-meal (Group B). Release onset for Group B was earlier than Group A (343min vs 448min). Group B tablets exhibited a clear residence period at the ileocaecal junction (ICJ) which was not observed in Group A. Prolonged residence at the ICJ is assumed to have increased hydration of the hydrogel layer surrounding the core tablet. Forces applied as the tablets progressed through the ICJ may have disrupted the hydrogel layer sufficiently to initiate radiolabel release. Conversely, Group A tablets moved rapidly through the AC to the TC, possibly minimising contact times with water pockets. Inadequate prior hydration of the hydrogel layer preventing access of pectinolytic enzymes and reduced fluid availability in the TC may have retarded tablet disintegration and radiolabel diffusion.

Evaluation of black tea gel and its protection potential against UV.

In this study, aqueous and alcoholic extracts of black tea were obtained. The black tea extracts were tested in vitro for their ultraviolet (UV) absorption profile. It was found that both extracts showed UV absorption and followed the same path based on the wavelength. Aqueous extract showed a stronger absorptivity per weight basis than the alcoholic extract of black tea. A peak was obtained between 250 and 300 nm. After 300 nm, UV absorption decreased fast towards 400 nm with a low absorptivity. The black tea aqueous extract was formulated as a gel with the help of a carbomer resin and tested in vivo in six subjects for evaluating its protection potential against the UV (200-400 nm) using an artificial UV source consisting of a high pressure metal halide discharge lamp. Based on erythema evaluation, it was found that erythema appeared after 4 h and reached a peak at 24 h on control site. On the contrary, no erythema was observed in any of the six subjects on black tea gel applied sites. Therefore, it was concluded that black tea gel protected the skin from a broad range UV (200-400 nm) radiation. The black tea gel can be safely applied in large amounts on large skin surfaces without any toxicological concerns.

Modelling of the solvent evaporation method for the preparation of controlled release acrylic microspheres using neural networks.

The purpose of the present study was to model the solvent evaporation procedure for the preparation of acrylic microspheres by using artificial neural networks (ANNs) to obtain an understanding of the selected preparative variables. Three preparative variables, the concentration of the dispersing agent (sucrose stearate), the stirring rate of emulsion system, and the ratio of polymers (Eudragit RS-L) were studied, each at different levels, as input variables. The response (output) variables examined to characterize microspheres and drug release were the size of the microspheres and T63.2%, the time at which 63.2% of drug is released. The results were also analysed by the multiple linear regression (MLR) to provide a comparison with the ANN methodology. Although both ANN and MLR methods were found to be similar in characterizing the process studied, the results showed that an ANN method gave a better prediction than the MLR method. For the size values of the microspheres, the predictability of the ANN model was quite high (R2 = 0.9602) based on the input variables. A relationship between these variables and size values of microspheres was also obtained by the MLR model (R2 = 0.9050). The performances of both models for the release data from microspheres based on the same input variables were at the level of 53%. According to the results, the ANN methodology can provide an alternative to the traditional regression methods, as a flexible and accurate method to study process and formulation factors.

Modeling of a roller-compaction process using neural networks and genetic algorithms.

In this study, roller-compaction of acetaminophene was studied to model the effect of binder type (hydroxypropyl methyl cellulose (HPMC), polyethylene glycol (PEG), Carbopol), binder concentration (5, 10 and 20%), number of roller-compaction passes (one or two), and extragranular microcrystalline cellulose addition on the properties of compressed tablets. Forty-two batches resulted from the experimental design. The artificial neural network methodology (ANN) along with genetic algorithms were used for data analysis and optimization. ANN and genetic models provided R2 values between 0.3593 and 0.9991 for measured responses. When a set of validation experiments was analyzed, genetic algorithm predictions of tablet characteristics were much better than the ANN. Optimization based on genetic algorithm showed that using HPMC at 20%, with two roller-compaction passes would produce mechanically acceptable acetaminophene tablets. PEG and carbopol would also produce acceptable tablets perhaps more suitable for sustained release applications. Using PEG as a binder had the additional advantage of not requiring an external lubricant during tablet manufacturing.

Evaulation of irritation potential of surfactant mixtures.

Irritation potential of sodium laureth sulfate (SLES) alone, and in combination with lauryl glucoside (LG), polysorbate 20 (PS) and cocoamidopropyl betaine (CAPB) was tested in 13 human subjects. Four main and six sub-formulations were prepared and evaluated. Formulations were applied to the forearm as a 24 h close patch study. Irritation was scored by two different methods using an in vivo clinical protocol based on visual scoring and on the stratum corneum capacitance measurement. Irritation was found to be dose dependent. At 2 mg/patch level ten subjects did not show any skin reaction. At 20 mg/patch level eleven subjects showed a broad range of skin irritation. The highest irritation was observed with the formula that contained SLES, LG, and cocamide DEA together. Among the sub-formulations, cocamide DEA showed the highest irritation grade. A statistically significant correlation was observed between visual, clinical and corneometer scores. It was concluded that the irritation potential of surfactants was related to the total surfactant concentration, application mode, and the thermodynamic activity of molecules in the solution as well as the chemical structure of the surfactant molecules.

Design and in vivo evaluation of ultrafine inorganic-oxide-containing-sunscreen formulations.

Ultrafine titanium dioxide, zinc oxide, and a 1:1 mixture of ZnO/TiO2 were used as 5% dispersions in sunscreen formulae. Three different carrier bases were evaluated for their accelerated stability and rheological properties with and without metal oxides based on sodium lauryl sulphate/polysorbate 80, triethanolamine stearate, and cetyl trimethyl ammonium chloride. All three bases showed thixotropic behaviour. Addition of metal oxides only affected the magnitude of viscosity not the viscoelastic behaviour. The cationic emulsion base was found to be the most stable to incorporate the microfine metal oxides, the others' viscosity values showing a significant drop in storage. The in vivo sun protection factors were determined on the cationic based emulsions in four human subjects using an UV source covering both UVA-UVB regions. The mean sun protection factors were found to be 5.03, 4.03, and 4.8 for TiO2, ZnO, and 1:1 ZnO/TiO2 respectively for 4 mg.cm-2 applications, the differences not being significant.

In vitro/in vivo evaluation of hydrochlorothiazide in experimental hydrochlorothiazide/triamterene combination tablets in beagle dogs.

The purpose of this study was to compare experimental formulations containing hydrochlorothiazide (CAS 58-93-5)/triamterene (HCT/TRI) in vitro and in vivo to a commercial tablet formulation (standard). The beagle dog was verified as a good model and was used for the in vivo studies. The commercial tablet and the experimental fast release formulation (FR) resulted in 100% release of HCT within 30 min in dissolution tests, whereas, the slow release formulation (SR) released only 54% HCT after 4 h. Relative bioavailability of the FR and SR formulations were 82 and 41%, respectively, compared to the commercial tablet. The experimental results indicate that HCT absorption occurs throughout the small intestine.