Detailed stability investigation of amorphous solid dispersions prepared by single-needle and high speed electrospinning.

In this research the long-term stability (one year) of amorphous solid dispersions (ASDs) prepared by high speed electrospinning was investigated at 25 °C/60% relative humidity (RH) (closed conditions) and 40 °C/75% RH (open conditions). Single needle electrospinning and film casting were applied as reference technologies. Itraconazole (ITR) was used as the model API in 40% concentration and the ASDs consisted of either one of the following polymers as a comparison: polyvinylpyrrolidone-vinyl acetate 6:4 copolymer (no hydrogen bonds between API and polymer) and hydroxypropyl methylcellulose (possible hydrogen bonds between oxo or tertiary nitrogen function of API and hydroxyl moiety of polymer). DSC, XRPD and dissolution characteristics of samples at 0, 3 and 12 months were investigated. In addition, Raman maps of certain electrospun ASDs were assessed to investigate crystallinity. A new chemometric method, based on Multivariate Curve Resolution-Alternating Least Squares algorithm, was developed to calculate the spectrum of amorphous ITR in the matrices and to determine the crystalline/amorphous ratio of aged samples. As it was expected ITR in single needle electrospun SDs was totally amorphous at the beginning, in addition hydroxypropyl methylcellulose could keep ITR in this form at 40 °C/75% RH up to one year due to the hydrogen bonds and high glass transition temperature of the SD. In polyvinylpyrrolidone-vinyl acetate matrix ITR remained amorphous at 25 °C/60% RH throughout one year. Materials prepared by scaled-up, high throughput version of electrospinning, which is compatible with pharmaceutical industry, also gained the same quality. Therefore these ASDs are industrially applicable and with an appropriate downstream process it would be possible to bring them to the market.

Combination of amlodipine 10 mg and valsartan 160 mg lowers blood pressure in patients with hypertension not controlled by an ACE inhibitor/CCB combination.

AIMS: This multicenter, open-label, single-arm trial assessed the efficacy of the combination of amlodipine 10 mg and valsartan 160 mg to provide additional blood pressure reduction and tolerability in patients with moderate hypertension not adequately responding to the combination of ramipril 5 mg and felodipine 5 mg. RESULTS: Of 133 patients treated for 5 weeks with ramipril 5 mg and felodipine 5 mg, 105 failed to achieve mean sitting systolic blood pressure <140 mmHg. These non-responders were then treated for an additional 5 weeks with amlodipine 10 mg and valsartan 160 mg, which resulted in clinically and statistically significant additional reductions in mean sitting systolic blood pressure of 15.4 mmHg (p<0.0001) and mean sitting diastolic blood pressure of 7.0 mmHg (p<0.0001). Adverse event rates were low with both treatment regimens. CONCLUSIONS: In hypertensive patients not controlled at 5 weeks by ramipril 5 mg and felodipine 5 mg, significant additional blood pressure reductions were observed after 5 weeks of treatment with amlodipine 10 mg and valsartan 160 mg. The combination of amlodipine 10 mg and valsartan 160 mg was well tolerated.

[Precocious puberty caused by a testicular Leydig cell tumor]. / Korai nemi érést okozó here Leydig-sejttumor.

Testicular tumors are very rare in boys, approximately 1.5% of these are Leydig cell tumors. The authors present a 4.5 year-old boy with Leydig cell tumor of left testis, which was associated with increased sex steroid production that caused precocious puberty. These tumors are benign processes in prepubertal children. Beyond the rarity of this case the authors would like to report about its diagnostic difficulties and testis-sparing remove of it. The plasma 17-hydroxyprogesterone levels provide the distinction between congenital adrenal hyperplasia and Leydig cell tumor in patient with precocious puberty.

Voiding disorders and unstable bladder in children.

A total of 42 neurologically normal children with different voiding problems have been studied urodynamically during the last 4 years. Seventeen patients had unstable bladder, with significantly decreased capacity. The degree of volume decrease depended on the severity of instability and on the type of micturition problems. Eight patients had trabeculation of the bladder wall and 2 had wide bladder neck. Six children had vesicoureteral reflux in 8 ureters. Eleven patients were treated with Ditropan. Four children had repeated cystomanometry after treatment. They had stable bladder and its capacity has increased.

Follow-up evaluation of anomalies of the vesicoureteric junction.

Anomalies of the vesicoureteric junction are important, particularly obstruction and reflux, as they may predispose to urinary tract infection. Over a 5-year period, 52 babies were referred with dilatation of the urinary tract detected antenatally or/and postnatally by ultrasound. Sixteen had an anomaly of the vesicoureteric junction: 9 had vesicoureteric reflux, 3 had ureteroceles, 1 had urethral stenosis with secondary reflux and 3 had stenosis of the vesicoureteric junction. Ten patients underwent 14 surgical procedures. The mean time to reconstructive surgery was 9.3 months. Ultrasonography showed regression of the dilatation in all patients who underwent surgery. Seven patients with minor dilatation are still under observation. In only 1 case was there loss of renal parenchyma. With conservative medical treatment the patients are 1 year old before reconstructive surgery is undertaken; with reflux, however, progression may indicate earlier surgery.

[Advantages and limitations of single-channel urodynamics in childhood]. / Egycsatornás urodynamia elönyei és korlátai gyermekkorban.

The simultaneous recording of urodynamic parameters and x-ray imaging of the lower urinary tract is the ideal technique for a complex investigation of the lower urinary tract morphology and function. The urodynamic and micturating cystourethrography findings were reviewed in 57 children. The causes of the examinations were recurrent urinary tract infection, voiding dysfunction and urinary tract dilatation by ultrasound. 53/57 patients had a clear cystomanometry results. 4 did not cooperate. 15/53 had unstable bladder. 34/57 had vesico-ureteric reflux. Unilateral reflux was more frequently noted in children with an unstable bladder. In cases of a stable bladder, bilateral reflux occurred more frequently. The ureteric reflux in children with unstable bladder should resolve with therapy to decrease bladder activity. Urodynamics is complementary rather than competitive with radiologic investigations. It is necessary to make micturating cystourethrography with cystomanometry.

[Pancreatic pseudocysts in children]. / Pancreas pseudocysták gyermekkorban.

Pancreas pseudocysts in childhood. On the basis of experience obtained with 9 patients treated over 31 years the authors publish the first comprehensive study in Hungary on the pancreas pseudocyst in childhood. Having reviewed their series and the medical literature main features and the possible prevention and management of this disease is outlined. Review of these patients with ultrasonography and chemistry tests is advised in order to follow-up the recovery and to screen the error in the glucose metabolism.

[Acetylator phenotype in spondylarthritis ankylopoietica]. / Acetilátor fenotípus vizsgálata spondylarthritis ankylopoeticában.

The authors studied the distribution of acetylator phenotypes among 136 AS patients (100 male, 36 female). 67 per cent of all patients were slow acetylators, 72 per cent of the males. Both rates are higher than that of the healthy Hungarian population. The authors draw attention to the clinical importance of investigating the acetylator type before sulphasalazine treatment because it may help in prescribing the effective dose and avoiding side effects.