DEVELOPMENT AND CHARACTERIZATION OF LORATADINE LIPOSOMAL GEL USING QbD APPROACH

Abstract

This study aimed to formulate, prepare and characterize a loratadine liposomal gel (LOR-L-G) using the Quality by Design (QbD) approach. The formulation variables and process parameters that influence the Critical Quality Attributes (CQAs) were identified using risk assessment. Five dependent variables were considered relevant for this study: particle size before and after extrusion, polydispersity index (PDI) before extrusion, loratadine (LOR) concentration and encapsulation efficiency (EE). A two-level full factorial design was performed in order to develop loratadine-loaded liposomes (LOR-L) with the desired Quality Target Product Profile (QTPP). Based on the results, the design space was generated and the optimum formulation was prepared. The in vitro drug release study aimed at measuring drug availability and revealed a prolonged release profile of LOR with a maximum concentration at 48 hours. LOR-L were incorporated into a Carbopol 940 gel base in order to obtain the final pharmaceutical product. The liposomal gel was characterized by viscosity, texture, spreadability and it was compared with a commercial product. The results indicated the applicability of the QbD approach in the development of LOR-L, and the obtained gel characteristics were suitable for a product useful in skin allergies. RezumatObiectivele studiului au fost formularea, prepararea și caracterizarea unui gel lipozomal cu loratadină (G-L-LOR) utilizând conceptul de calitate prin design (QbD). S-au identificat variabilele de formulare și parametrii de proces responsabili de afectarea atributelor critice de calitate ale lipozomilor cu loratadină (L-LOR) prin efectuarea analizei de risc. Au fost luate în considerare 5 variabile dependente, anume mărimea particulelor înainte și după extrudare, indicele de polidispersie (PDI) înainte de extrudare, concentrația de loratadină (LOR) și eficiența încorporării (EE). S-a folosit un plan experimental cu două niveluri pentru dezvoltarea L-LOR care să dețină caracteristicile de calitate dorite. Pe baza rezultatelor obținute s-a determinat domeniul optim și a fost preparată formularea optimă. S-a efectuat studiul de cedare in vitro, care a demonstrat o cedare prelungită a LOR din formulările lipozomale, cu o concentrație maximă la 48 ore. În vederea obținerii produsului farmaceutic final, lipozomii au fost încorporați într-o bază de gel de Carbopol 940. Gelul lipozomal a fost caracterizat din punct de vedere al vâscozității, texturii, capacității de întindere și a fost comparat cu un gel existent pe piață. Rezultatele au demonstrat aplicabilitatea conceptului de calitate prin design în dezvoltarea L-LOR, iar caracteristicile gelului obținut au fost potrivite pentru aplicarea acestuia în alergiile cutanate.

Quality by Design Approach for the Development of Salinomycin and Gemcitabine Combination Therapy Liposomes for Colorectal Cancer

“…The QbD risk assessment implies an interdependence rating established between the CMAs-CQAs and/or CPPs-CQAs, measuring the impact of each quality attribute on the final product [32,33]. Risk estimation matrix (REM) is a risk rating tool constructed for CMAs and/or CPPs commonly using a three-grade scale (low, medium and high) to describe the criticality in relation to the CQAs [34].…”

Chemical Profile and Biological Effects of an Herbal Mixture for the Development of an Oil-in-Water Cream

“…All these characteristics were chosen to obtain a favourable sensory profile for increased patients’ acceptability, taking into consideration the longer period of use in seborrheic dermatitis. Table 9 contains the QTPP and QAs considered relevant for this study, which were established based on previously reported studies that use similar settings [ 14 , 59 ].…”

“…Each of these criteria was attributed to each CPP (formulation factors and process parameters) and was ranked from 1 to 5 on a scale: the occurrence (O) was evaluated as 5 for frequent, 4 for probable, 3 for occasional, 2 for remote, and 1 for improbable; the severity (S), was ranked as 5 for catastrophic, 4 for critical, 3 for serious, 2 for minor, and 1 for negligible; detectability (D) was given a score of 5 for hard to detect, 4 for low chance of detection, 3 for moderately detectable, 2 for highly detectable, and 1 for easily detectable. The risk score has been revealed as risk priority number (RPN), by multiplying these three attributes [ 59 ].…”

Fabrication of nanostructured lipid carriers ocugel for enhancing Loratadine used in treatment of COVID-19 related symptoms: statistical optimization, in-vitro, ex-vivo, and in-vivo studies evaluation

“…The total volume was modified to 100 ml by purified water including LORA-NLCs. The gel was left overnight in the refrigerator, LORA-NLCs Ocugel had a final concentration of 1 mg/g LORA (Toma et al, 2022 ).…”