In Vivo Assessment of Parenteral Formulations of Oligo(3-Hydroxybutyric Acid) Conjugates with the Model Compound Ibuprofen

Polymer-drug conjugates have gained significant attention as pro-drugs releasing an active substance as a result of enzymatic hydrolysis in physiological environment. In this study, a conjugate of 3-hydroxybutyric acid oligomers with a carboxylic acid group-bearing model drug (ibuprofen) was evaluated in vivo as a potential pro-drug for parenteral administration. Two different formulations, an oily solution and an o/w emulsion were prepared and administered intramuscularly (IM) to rabbits in a dose corresponding to 40 mg of ibuprofen/kilogramme. The concentration of ibuprofen in blood plasma was analysed by HPLC, following solid–phase extraction and using indometacin as internal standard (detection limit, 0.05 μg/ml). No significant differences in the pharmacokinetic parameters (Cmax, Tmax, AUC) were observed between the two tested formulations of the 3-hydroxybutyric acid conjugate. In comparison to the non-conjugated drug in oily solution, the relative bioavailability of ibuprofen conjugates from oily solution, and o/w emulsion was reduced to 17% and 10%, respectively. The 3-hydroxybutyric acid formulations released the active substance over a significantly extended period of time with ibuprofen still being detectable 24 h post-injection, whereas the free compound was almost completely eliminated as early as 6 h after administration. The conjugates remained in a muscle tissue for a prolonged time and can hence be considered as sustained release systems for carboxylic acid derivatives

The use of compounded dispersing media for extemporaneous pediatric syrups with candesartan cilexetil and valsartan

Available tablets or capsules for adults are often used to prepare extemporaneously formulated medicines appropriate for children. The most acceptable drug forms in pediatric population are oral liquids and pharmacists use commercial dispersing media to compound syrups from an active substance or from tablets available on the market. In many countries ready-to-use dispersing media are not available or refunded, but pharmacists can use other compounded media, providing their compatibility and stability are proven. The aim of this study was to formulate and evaluate the stability of syrups with candesartan cilexetil (1 mg mL–1) and valsartan (4 mg mL–1) extemporaneously prepared using commercial tablets (Diovan® and Atacand®). The following three different suspending media, which could be easily made in a pharmacy, were investigated: V1 – with xanthan gum (0.5 %), V2 – the USP/NF vehicle for oral solution and V3 – the medium based on a simple sucrose syrup. The stability of preparations was studied during 35 days of storage in a dark place at controlled temperature of 25 and 4 ºC. During the study, microscopic observation was carried out and pH, viscosity, and concentration of candesartan cilexetil and valsartan were analyzed. Syrups with valsartan prepared with V2 and V3 media were stable for 3 or 4 weeks when stored at 25 °C, while syrups with candesartan were stable for as long as 35 days. For syrups prepared using V1 medium, the14-day expiry date was not achieved because of microbial deterioration

Use of compounded dispersing media for extemporaneous pediatric syrups with candesartan cilexetil and valsartan

Available tablets or capsules for adults are often used to prepare extemporaneously formulated medicines appropriate for children. The most acceptable drug forms in pediatric population are oral liquids and pharmacists use commercial dispersing media to compound syrups from an active substance or from tablets available on the market. In many countries ready-to-use dispersing media are not available or refunded, but pharmacists can use other compounded media, providing their compatibility and stability are proven. The aim of this study was to formulate and evaluate the stability of syrups with candesartan cilexetil (1 mg mL-1) and valsartan (4 mg mL-1) extemporaneously prepared using commercial tablets (Diovan® and Atacand®). The following three different suspending media, which could be easily made in a pharmacy, were investigated: V1 - with xanthan gum (0.5 %), V2 - the USP/NF vehicle for oral solution and V3 - the medium based on a simple sucrose syrup. The stability of preparations was studied during 35 days of storage in a dark place at controlled temperature of 25 and 4 °C. During the study, microscopic observation was carried out and pH, viscosity, and concentration of candesartan cilexetil and valsartan were analyzed. Syrups with valsartan prepared with V2 and V3 media were stable for 3 or 4 weeks when stored at 25 °C, while syrups with candesartan were stable for as long as 35 days. For syrups prepared using V1 medium, the 14-day expiry date was not achieved because of microbial deterioration

Use of compounded dispersing media for extemporaneous pediatric syrups with candesartan cilexetil and valsartan

Available tablets or capsules for adults are often used to prepare extemporaneously formulated medicines appropriate for children. The most acceptable drug forms in pediatric population are oral liquids and pharmacists use commercial dispersing media to compound syrups from an active substance or from tablets available on the market. In many countries ready-to-use dispersing media are not available or refunded, but pharmacists can use other compounded media, providing their compatibility and stability are proven. The aim of this study was to formulate and evaluate the stability of syrups with candesartan cilexetil (1 mg mL–1) and valsartan (4 mg mL–1) extemporaneously prepared using commercial tablets (Diovan® and Atacand®). The following three different suspending media, which could be easily made in a pharmacy, were investigated: V1 – with xanthan gum (0.5 %), V2 – the USP/NF vehicle for oral solution and V3 – the medium based on a simple sucrose syrup. The stability of preparations was studied during 35 days of storage in a dark place at controlled temperature of 25 and 4 ºC. During the study, microscopic observation was carried out and pH, viscosity, and concentration of candesartan cilexetil and valsartan were analyzed. Syrups with valsartan prepared with V2 and V3 media were stable for 3 or 4 weeks when stored at 25 °C, while syrups with candesartan were stable for as long as 35 days. For syrups prepared using V1 medium, the14-day expiry date was not achieved because of microbial deterioration

Technology of Orodispersible Polymer Films with Micronized Loratadine—Influence of Different Drug Loadings on Film Properties

The production of orodispersible films (ODFs) with suspended insoluble drug substances is still a challenge, mainly due to the difficulty associated with achieving a proper homogeneity and mechanical properties of the films. Hypromellose (HPMC) and a mixture of polyvinyl alcohol (AP) and povidone (PVP) were compared in terms of their suitability for ODFs incorporating suspended micronized loratadine (LO) in a concentration range of 10%–40%. In a planetary mixer (Thinky), a uniform dispersion of LO in an aqueous viscous casting solution was obtained. The suspended LO particles caused dose-dependent changes in the viscosity of the casting mass and affected the mechanical quality of ODFs. Drug concentrations higher than 30% reduced the film flexibility and tear resistance, depending on the polymer type. LO films with a thickness of 100 µm disintegrated within 60-100 s, with no significant influence of the LO content in the range 10%–30%. HPMC films, regardless of the drug concentration, met the pharmacopoeial requirements regarding the uniformity of the drug content. AP/PVP films were too elastic, and the drug content uniformity was not achieved. The conclusion is that, using an HPMC matrix, it is possible to obtain a high load of a poorly water-soluble drug (30% of dry film mass corresponds to a dose of 5 mg per 1.5 cm2) in ODFs characterized by proper physical characteristics

3D Printing of Mini Tablets for Pediatric Use

In the treatment of pediatric diseases, suitable dosages and dosage forms are often not available for an adequate therapy. The use of innovative additive manufacturing techniques offers the possibility of producing pediatric dosage forms. In this study, the production of mini tablets using fused deposition modeling (FDM)-based 3D printing was investigated. Two pediatric drugs, caffeine and propranolol hydrochloride, were successfully processed into filaments using hyprolose and hypromellose as polymers. Subsequently, mini tablets with diameters between 1.5 and 4.0 mm were printed and characterized using optical and thermal analysis methods. By varying the number of mini tablets applied and by varying the diameter, we were able to achieve different release behaviors. This work highlights the potential value of FDM 3D printing for the on-demand production of patient individualized, small-scale batches of pediatric dosage forms