The strategic relevance of manufacturing technology : an overall quality concept to promote innovation preventing drug shortage

Manufacturing is the bridge between research and patient: without product, there is no clinical outcome. Shortage has a variety of causes, in this paper we analyse only causes related to manufacturing technology and we use shortage as a paradigm highliting the relevance of Pharmaceutical Technology. Product and process complexity and capacity issues are the main challenge for the Pharmaceutical Industry Supply chain. Manufacturing Technology should be acknowledged as a R&D step and as a very important matter during University degree in Pharmacy and related disciplines, promoting collaboration between Academia and Industry, measured during HTA step and rewarded in terms of price and reimbursement. The above elements are not yet properly recognised, and manufacturing technology is taken in to consideration only when a shortage is in place. In a previous work, Panzitta et al. proposed to perform a full technology assessment at the Health Technological Assessment stage, evaluating three main technical aspects of a medicine: manufacturing process, physicochemical properties, and formulation characteristics. In this paper, we develop the concept of manufacturing appraisal, providing a technical overview of upcoming challenges, a risk based approach and an economic picture of shortage costs. We develop also an overall quality concept, not limited to GMP factors but broaden to all elements leading to a robust supply and promoting technical innovation

Dizajniranje i vrednovanje okularnih umetaka moksifloksacin hidroklorida

The objective of the present investigation was to prepare and evaluate ocular inserts of moxifloxacin. An ocular insert was made from an aqueous dispersion of moxifloxacin, sodium alginate, polyvinyl alcohol, and dibutyl phthalate by the film casting method. The ocular insert (5.5 mm diameter) was cross-linked by CaCl2 and was coated with Eudragit S-100, RL-100, RS-100, E-100 or Eudragit L-100. The in vitro drug drainage/permeation studies were carried out using an all-glass modified Franz diffusion cell. The drug concentration and mucoadhesion time of the ocular insert were found satisfactory. Cross-linking and coating with polymers extended the drainage from inserts. The cross-linked ocular insert coated with Eudragit RL-100 showed maximum drug permeation compared to other formulations.Cilj rada bio je priprava i evaluacija okularnih umetaka moksifloksacina. Okularni umetak izrađen je od vodene suspenzije moksifloksacina, natrijevog alginata, polivinilnog alkohola i dibutil-ftalata metodom odlijevanja filma. Okularni umetak (promjera 5,5 mm) umrežen je pomoću CaCl2 i obložen Eudragitom S-100, RL-100, RS-100, E-100 ili Eudragit L-100. In vitro drenaža/permeacija lijeka proučavana je koristeći staklenu modificiranu Franzovu difuzijsku ćeliju. Koncentracija lijeka i vrijeme mukoadhezije okularnih umetaka bili su zadovoljavajući. Umrežavanje i oblaganje polimerima produljilo je drenažu iz umetaka. Umreženi okularni umetci obloženi s Eudragit RL-100 pokazali su veću permeaciju lijeka u odnosu na ostale pripravke

Razvoj matriksnih sustava za transdermalnu isporuku pentazocina: In vitro/in vivo ispitivanje

The present study aimed to develop hydroxypropyl methylcellulose based transdermal delivery of pentazocine. In formulations containing lower proportions of polymer, the drug released followed the Higuchi kinetics while, with an increase in polymer content, it followed the zero-order release kinetics. Release exponent (n) values imply that the release of pentazocine from matrices was non-Fickian. FT-IR, DSC and XRD studies indicated no interaction between drug and polymer. The in vitro dissolution rate constant, dissolution half-life and pharmacokinetic parameters (Cmax, tmax, AUC(s), t1/2, Kel, and MRT) were evaluated statistically by two-way ANOVA. A significant difference was observed between but not within the tested products. Statistically, a good correlation was found between per cent of drug absorbed from patches vs. Cmax, and AUC(s). A good correlation was also observed when per cent drug released was correlated with the blood drug concentration obtained at the same time point. The results of this study indicate that the polymeric matrix films of pentazocine hold potential for transdermal drug delivery.U radu je opisan razvoj transdermalnih sustava na bazi hidroksipropil metilceluloze za isporuku pentazocina. U pripravcima koji sadrže manje udjele polimera, otpuštanje lijeka slijedilo je Higuchijevu kinetiku. Međutim, ako je udio polimera veći oslobađanje je najbolje odgovaralo kinetici nultog reda. Vrijednost eksponenta n implicira da oslobađanje pentazocina iz matriksa nije po Fickovom zakonu. FT-IR, DSC i X RD studije ukazuju da nema interakcije između ljekovite tvari i polimera. In vitro konstanta oslobađanja, poluvrijeme oslobađanja i farmakokinetički parametri (Cmax, tmax, AUC(s), t1/2, Kel, i MRT) procijenjeni su statistički koristeći ANOVA program. Značajna razlika primijećena je između, ali ne i unutar testiranih pripravaka. Pronađena je dobra korelacija između lijeka apsorbiranog iz flastera i Cmax i AUC(s) te oslobođenog lijeka i koncentracije lijeka u krvi. Rezultati ukazuju da su polimerni matriksni filmovi pentazocina potencijalno dobri sustavi za transdermalnu primjenu lijeka

Synthesis of (cinnamate-zinc layered hydroxide) intercalation compound for sunscreen application

Background: Zinc layered hydroxide (ZLH) intercalated with cinnamate, an anionic form of cinnamic acid (CA), an efficient UVA and UVB absorber, have been synthesized by direct method using zinc oxide (ZnO) and cinnamic acid as the precursor. Results: The resulting obtained intercalation compound, ZCA, showed a basal spacing of 23.9 Å as a result of cinnamate intercalated in a bilayer arrangement between the interlayer spaces of ZLH with estimated percentage loading of cinnamate of about 40.4 % w/w. The UV–vis absorption spectrum of the intercalation compound showed excellent UVA and UVB absorption ability. Retention of cinnamate in ZLH interlayers was tested against media usually came across with sunscreen usage to show low release over an extended period of time. MTT assay of the intercalation compound on human dermal fibroblast (HDF) cells showed cytotoxicity of ZCA to be concentration dependent and is overall less toxic than its precursor, ZnO. Conclusions: (Cinnamate-zinc layered hydroxide) intercalation compound is suitable to be used as a safe and effective sunscreen with long UV protection effect

Razvoj i karakterizacija mukoadhezivnih flastera salbutamol sulfata za jednosmjernu bukalnu isporuku

Buccal patches of salbutamol sulfate were prepared using five different water soluble polymers in various proportions and combinations using PEG-400/PG as plasticizers. A 32 full factorial design was used to design the experiments for each polymer combination. Patches were laminated on one side with a water impermeable backing layer for unidirectional drug release. The thickness of medicated patches ranged between 0.2 and 0.4 mm and showed an increase in mass whenever PEG-400 was used as plasticizer. The surface pH of all patches approached neutral. Eight formulations which had shown high folding endurance (> 300) were selected for evaluation. Patches prepared with PEG-400 showed a high swelling index. The residence time of the tested patches ranged between 105 and 130 min. Formulations A10, A32, B10 and B32 fitted the Higuchi model best, whereas formulations A19 and B19 showed super case II transport drug release. Stability studies indicated that there was no change in the chemical and physical characteristics during the test period of 6 months.U radu je opisana priprava flastera za bukalnu primjenu upotrebom različitih omjera pet vodotopljivih polimera i PEG-400/PG kao plastifikatora. Potpuni 32 faktorijalni dizajn upotrebljen je za dizajniranje eksperimenata za svaku kombinaciju polimera. Flasteri su postavljeni na jednu stranu usta s vodonepropusnom podlogom, koja omogućava jednosmjerno oslobađanje lijeka. Debljina flastera varirala je između 0,2 i 0,4 nm. Flasteri s PEG-400 bili su malo veće mase. pH na površini svih flastera bio je blizu neutralnog. Osam pripravaka vrlo otpornih na presavijanje (300) izabrano je za daljnju evaluaciju. Flasteri pripravljeni s PEG 400 imali su veliku sposobnost bubrenja. Flasteri su se zadržali na mjestu primjene između 105 i 130 min. Pripravci A10, A32, B10 i B32 najbolje su slijedili Higuchijev model, dok su pripravci A19 i B19 pokazivali anomalno oslobađanje koje ne slijedi Fickov zakon. Ispitivanje stabilnosti pokazalo je da ne postoje promjene u kemijskim i fizikalnim svojstvima pripravaka tijekom 6 mjeseci

Hydrogel blends with adjustable properties as patches for transdermal delivery.

The effect of different preparation parameters were analyzed with respect to the rheological and pharmaceutical characteristics of hydrogel blend patches, as transdermal delivery formulation. Mixtures of pectin and gelatin were employed for the production of patches, with adjustable properties, following a two-step gelation procedure. The first gelation, a thermal one, is trigged by the presence of gelatin, whereas, the second gelation, an ionic one, is due to the formation of the typical egg box structure of pectin. In particular, the patch structural properties were assessed by oscillation stress sweep measurements which provided information concerning their viscolelastic properties. In addition, different modalities for drug loading were analyzed with respect to drug homogeneous distribution; testosterone was employed as model drug for transdermal administration. Finally, the performances of the produced transdermal patches were studied, in term of reproducibility and reliability, by determination of in vitro drug release profiles

Rheological and functional characterization of new antiinflammatory delivery systems designed for buccal administration

delivery systems designed for buccal administratio

Studies on annelated 1,4-benzothiazines and 1,5-benzothiazepines .10. Synthesis and inhibition of benzodiazepine receptor binding of new 1,4-thiazine and 1,5-thiazepine polycondensed heterocycles with steroidal structure

Some naphthol [1,2,-b]-s-triazolo[4,3-d]-1,4-thiazine and 1,5-thiazepine and s-triazolo[4',3'-4,5]-1, ,4-thiazino[3,2-c]quinoline derivatives have been synthesized and tested for their ability to displace [H-3]RO 15-1788 binding from bovine brain membranes. Several compounds showed moderate binding affinity for the benzodiazepine receptor