Izrada i karakterizacija IPN alginatnih i želatinskih mikrogelova s tramadolom: Optimiranje pomoću metode odzivnih površina

Tramadol-loaded interpenetrating polymer network (IPN) alginate-gelatin (AG) microgels (MG) were prepared by the chemical cross-linking technique with glutaraldehyde as cross-linking agent and were optimized using response surfaces. A central composite design for 2 factors, at 3 levels each, was employed to evaluate the effect of critical formulation variables, namely the amount of gelatin (X1) and glutaraldehyde (X2) on geometric mean diameter, encapsulation efficiency, diffusion coefficient (D), amount of mucin adsorbed per unit mass (Qe) and 50 % drug release time (t50). Microgels with average particle size in the range of 44.31102.41 m were obtained. Drug encapsulation up to 86.5 % was achieved. MGs were characterized by FT-IR spectroscopy to assess formation of the IPN structure and differential scanning calorimetry (DSC) was performed to understand the nature of drug dispersion after encapsulation into IPN microgels. Both equilibrium and dynamic swelling studies were performed in pH 7.4 phosphate buffer. Diffusion coefficients and exponents for water transport were determined using an empirical equation. The mucoadhesive properties of MGs were evaluated in aqueous solution by measuring the mucin adsorbed on MGs. Adsorption isotherms were constructed and fitted with Freundlich and Langmuir equations. In vitro release studies indicated the dependence of drug release on the extent of crosslinking and amount of gelatin used in preparing IPNs. The release rates were fitted to power law equation and Higuchi’s model to compute the various drug transport parameters, n value ranged from 0.4055 to 0.5754, suggesting that release may vary from Fickian to quasi-Fickian depending upon variation in the formulation composition.Interpenetrirajući umreženi polimerni (IPN) alginatno-želatinski (AG) mikrogelovi (MG) tramadola pripravljeni su metodom umrežavanja koristeći glutaraldehid kao sredstvo za umrežavanje. Pripravci su optimirani pomoću odzivnih površina. Kompozitini dizajn s dva faktora na tri nivoa upotrijebljen je za procjenu kritičnih formulacijskih varijabli: praćen je utjecaj količine želatine (X1) i glutaraldehida (X2) na prosječnu veličinu čestica, sposobnost kapsuliranja, koeficijent difuzije (D), količinu adsorbiranog mucina po jedinici mase (Qe) i vrijeme potrebno za oslobađanje 50 % lijeka (t50). Dobiveni su mikrogelovi prosječne veličine čestica od 44,31 do 102,41 m, a maksimalno postignuto vezanje lijeka bilo je 86,5 %. Mikrogelovi su karakterizirani FT-IR spektroskopijom i diferencijalnom pretražnom kalorimetrijom (DSC). Ravnotežne i dinamičke studije bubrenja provedene su u fosfatnom puferu pH 7,4. Koeficijenti difuzije i eksponenti za transport vode određeni su pomoću empirijske jednadžbe. Mukoadhezivna svojstva MGs evaluirana su u vodenoj otopini mjerenjem adsorpcije mucina na mikrogelove. Konstruirane su adsorpcijske izoterme i uspoređene s Freudlichovim i Langmuirovim jednadžbama. Pokusi in vitro pokazuju da oslobađanje ljekovite tvari ovisi o stupnju umreženja i količini želatine upotrijebljene u pripravi IPN. Vrijednosti oslobađanja uvrštene su u jednadžbu zakona potencije i u Higuchijev model kako bi se izračunali razni parametri prijenosa lijeka; n vrijednosti bile su između 0,4055 i 0,5754, što ukazuje na to da oslobađanje varira od Fickovog do kvazi-Fickovog, ovisno o sastavu pripravka

Natural and Synthetic Polymers as Inhibitors of Drug Efflux Pumps

Inhibition of efflux pumps is an emerging approach in cancer therapy and drug delivery. Since it has been discovered that polymeric pharmaceutical excipients such as Tweens® or Pluronics® can inhibit efflux pumps, various other polymers have been investigated regarding their potential efflux pump inhibitory activity. Among them are polysaccharides, polyethylene glycols and derivatives, amphiphilic block copolymers, dendrimers and thiolated polymers. In the current review article, natural and synthetic polymers that are capable of inhibiting efflux pumps as well as their application in cancer therapy and drug delivery are discussed

Current challenges and future perspectives in oral absorption research: An opinion of the UNGAP network

Although oral drug delivery is the preferred administration route and has been used for centuries, modern drug discovery and development pipelines challenge conventional formulation approaches and highlight the insufficient mechanistic understanding of processes critical to oral drug absorption. This review presents the opinion of UNGAP scientists on four key themes across the oral absorption landscape: (1) specific patient populations, (2) regional differences in the gastrointestinal tract, (3) advanced formulations and (4) food-drug interactions. The differences of oral absorption in pediatric and geriatric populations, the specific issues in colonic absorption, the formulation approaches for poorly water-soluble (small molecules) and poorly permeable (peptides, RNA etc.) drugs, as well as the vast realm of food effects, are some of the topics discussed in detail. The identified controversies and gaps in the current understanding of gastrointestinal absorption-related processes are used to create a roadmap for the future of oral drug absorption research

Non-Invasive Oligonucleotide Delivery System Based on a Thiolated Polymer: Development and In Vitro Evaluation

It was the purpose of this study to develop an oral oligonucleotide delivery system based on thiolated polymer/ reduced glutathione (GSH) system providing protective effect towards nucleases, permeation enhancement and controlled drug release. [...