Investigating the Impact of Co-processed Excipients on the Formulation of Bromhexine Hydrochloride Orally Disintegrating Tablets (ODTs).

PURPOSE: Orodispersible tablets (orally disintegrating tablets, ODTs) have been used in pharmacotherapy for over 20 years since they overcome the problems with swallowing solid dosage forms. The successful formula manufactured by direct compression shall ensure acceptable mechanical strength and short disintegration time. Our research aimed to develop ODTs containing bromhexine hydrochloride suitable for registration in accordance with EMA requirements. METHODS: We examined the performance of five multifunctional co-processed excipients, i.e., F-Melt® C, F-Melt® M, Ludiflash®, Pharmaburst® 500 and Prosolv® ODT G2 as well as self-prepared physical blend of directly compressible excipients. We tested powder flow, true density, compaction characteristics and tableting speed sensitivity. RESULTS: The manufacturability studies confirmed that all the co-processed excipients are very effective as the ODT formula constituents. We noticed superior properties of both F-Melt's®, expressed by good mechanical strength of tablets and short disintegration time. Ludiflash® showed excellent performance due to low works of plastic deformation, elastic recovery and ejection. However, the tablets released less than 30% of the drug. Also, the self-prepared blend of excipients was found sufficient for ODT application and successfully transferred to production scale. Outcome of the scale-up trial revealed that the tablets complied with compendial requirements for orodispersible tablets. CONCLUSIONS: We proved that the active ingredient cannot be absorbed in oral cavity and its dissolution profiles in media representing upper part of gastrointestinal tract are similar to marketed immediate release drug product. In our opinion, the developed formula is suitable for registration within the well-established use procedure without necessity of bioequivalence testing.

Assessing Historical Mining and Smelting Effects on Heavy Metal Pollution of River Systems over Span of Two Decades.

Research was conducted on the most polluted river system in Poland, impacted by active and historical mining. Bottom sediment, suspended particulate matter and river water were collected in 2014 from Przemsza river and its tributaries. Sampling points remained the same as those chosen in a 1995 study. This allowed the comparison of heavy metal accumulation in bottom sediment over a span of almost two decades. It was concluded that Przemsza river water and its tributaries are heavily contaminated with the following (in µg/dm3): Pb (0.99-145.7), Zn (48-5020), and Cd 0.12-12.72). Concentrations of metals in bottom sediment exceeded the background values by a factor of several hundred (100 times for Zn, 150 times for Pb, and 240 times for Cd). The arithmetic mean for metal concentration in fractions <63 µm sampled in 2014 has remained comparable to the level found in 1995 (in mg/kg): Zn 16,918 and 13,505, Pb 4177 and 4758, and Cd 92 and 134. It was determined that 20-50% more metals have accumulated in suspended matter, rather than in bottom sediment (in mg/kg): 20,498 Zn, Pb 5170, and 164 Cd. This exceeds the limits of the most polluted LAWA Class IV classification. Since the concentrations of Zn, Pb, and Cd increase drastically after the outlet of the Przemsza into the Vistula, it was concluded that river Przemsza is the cause of significant degradation of Vistula's bottom sediment and suspended matter. A two-decade legacy of extremely high contamination of the Przemsza river sediments has persisted despite decreasing mining and smelting activity in the vicinity.