- Development and characterization of a mucoadhesive sublingual formulation for pain control: extemporaneous oxycodone films in personalized therapy. [Journal Article]
- DDDrug Dev Ind Pharm 2017 Jan 11; :1-29
- CONCLUSIONS: The obtained films showed excellent drug content uniformity and stability and rapid drug release, which, at 8 min, ranged from 60 to 80%. All films presented satisfactory mucoadhesive and mechanical properties, also confirmed by a test on healthy volunteers, who did not experience irritation or mucosa damages. Pectin films based on pectin at lower degrees of esterification have been further evaluated to study the influence of two different amounts of drug on the physicochemical properties of the formulation. A slight reduction of elasticity has been observed in films containing a higher drug dose, nevertheless the formulation maintained satisfactory flexibility and resistance to elongation.HPC and PC sublingual films, obtained by a simple casting method, could be proposed to realize personalized hospital pharmacy preparations on a small scale.
- Development of a fast, lean and agile direct pelletization process using experimental design techniques. [Journal Article]
- DDDrug Dev Ind Pharm 2017 Jan 05; :1-13
- A novel hot melt direct pelletization method was developed, characterized and optimized, using statistical thinking and experimental design tools. Mixtures of carnauba wax (CW) and HPMC K100M were sp...
A novel hot melt direct pelletization method was developed, characterized and optimized, using statistical thinking and experimental design tools. Mixtures of carnauba wax (CW) and HPMC K100M were spheronized using melted gelucire 50-13 as a binding material (BM). Experimentation was performed sequentially; a fractional factorial design was set up initially to screen the factors affecting the process, namely spray rate, quantity of BM, rotor speed, type of rotor disk, lubricant-glidant presence, additional spheronization time, powder feeding rate and quantity. From the eight factors assessed, three were further studied during process optimization (spray rate, quantity of BM and powder feeding rate), at different ratios of the solid mixture of CW and HPMC K100M. The study demonstrated that the novel hot melt process is fast, efficient, reproducible and predictable. Therefore, it can be adopted in a lean and agile manufacturing setting for the production of flexible pellet dosage forms with various release rates easily customized between immediate and modified delivery.
- Monoclonal antibodies: formulations of marketed products and recent advances in novel delivery system. [Journal Article]
- DDDrug Dev Ind Pharm 2017 Jan 04; :1-39
- Monoclonal antibodies (mAbs) are extensively employed for disease diagnosis and treatment because of their high homogeneity and antigen specificity. In recent years, important outcomes have been achi...
Monoclonal antibodies (mAbs) are extensively employed for disease diagnosis and treatment because of their high homogeneity and antigen specificity. In recent years, important outcomes have been achieved with mAbs due to their admirable therapeutic efficacy and relatively rare side effects. In clinical practice, several mAb products have been approved by regulatory entities, but their formulations have been highly specific given the complex structure and proteinaceous nature of mAbs. Thus, a great deal of attention has focused on formulations. An increasing number of novel delivery systems have been exploited to optimize the application of mAbs. In this article, the formulations, dosages, origins and administration routes of available mAbs approved by the Food and Drug Administration (FDA) are summarized and categorized. Key issues involved in formulation, processing, and storage are addressed as well as other challenges in achieving effective mAb delivery. Finally, recent advances in delivering mAbs in their most bioavailable forms are also briefly reviewed.
- Investigations on pharmacokinetics and biodistribution of polymeric and solid lipid nanoparticulate systems of atypical antipsychotic drug: Effect of material used and surface modification. [Journal Article]
- DDDrug Dev Ind Pharm 2017 Jan 03; :1-25
- The present study focuses on the effect of material used for the preparation of nanoparticulate systems (NP) and surface modification on the pharmacokinetics and biodistribution of atypical antipsych...
The present study focuses on the effect of material used for the preparation of nanoparticulate systems (NP) and surface modification on the pharmacokinetics and biodistribution of atypical antipsychotic, Olanzapine (OLN). Nanoparticulate carriers of OLN were prepared from two different materials such as polymer (polycaprolactone) and solid lipid (Glyceryl monostearate). These systems were further surface modified with surfactant, Polysorbate 80 and studied for pharmacokinetics-biodistribution in wistar rats using in-house developed bioanalytical methods. The pharmacokinetics and biodistribution studies resulted in a modified and varied distribution of nanoparticulate systems with higher area under curve (AUC) values along with prolonged residence time of OLN in the rat blood circulation. The distribution of OLN to the brain was significantly enhanced with surfactant surface modified nanoparticulate systems, followed by non surface modified nanoparticulate formulations as compared with pure OLN solution. Biodistribution study demonstrated a low uptake of obtained nanoparticulate systems by kidney and heart, thereby decreasing the nephrotoxicity and adverse cardiovascular effects. By coating the NP with surfactant, uptake of macrophage was found to be reduced. Thus, our studies confirmed that the biodistribution OLN could be modified effectively by incorporating in nanoparticulate drug delivery systems prepared from different materials and surface modifications. A judicious selection of materials used for the preparation of delivery carriers and surface modifications would help to design a most efficient drug delivery system with better therapeutic efficacy.
- Freeze-drying optimization of polymeric nanoparticles for ocular Flurbiprofen delivery: effect of protectant agents and critical process parameters on long-term stability. [Journal Article]
- DDDrug Dev Ind Pharm 2017 Jan 03; :1-37
- CONCLUSIONS: An optimal freeze dried ocular formulation was achieved. Evidently, the successful design of this promising colloidal system resulted from rational cooperation between a good formulation and the right conditions in the freeze-drying process.
- Hyaluronic acid-coated cationic nanostructured lipid carriers for oral vincristine sulfate delivery. [Journal Article]
- DDDrug Dev Ind Pharm 2017 Jan 08; :1-10
- The goal of this research is to structure a hyaluronic acid modified nanostructured lipid carrier (HA-NLCs) for vincristine sulfate (VCR) delivery, and detect its efficiency to improve the oral bioav...
The goal of this research is to structure a hyaluronic acid modified nanostructured lipid carrier (HA-NLCs) for vincristine sulfate (VCR) delivery, and detect its efficiency to improve the oral bioavailability. Emulsion solvent evaporation method was used to prepare the HA-NLCs nanoparticles. The particle size, zeta potential and entrapment efficiency of VCR-NLCs and HA-NLCs were 187 ± 3.52 nm, -8.61 ± 1.29 mV, 33.12 ± 1.16% and 192 ± 4.41 nm, -32.82 ± 2.64 mV, 34.41 ± 2.21%, respectively. HA-NLCs could significantly improve the cellular uptake efficiency and cytotoxicity in MCF-7 cells than other VCR formulations. The expressions of apoptosis related protein Caspase-3, Caspase-9, Bax and Bcl-2 were estimated by western blot assay in MCF-7 cells, and HA-NLCs exhibited the strongest effect in promoting cell apoptosis. The pharmacokinetics of HA-NLCs was evaluated in Sprague-Dawley male rats and the relative oral bioavailability of HA-NLCs and VCR-NLCs was improved about 1.8-fold and two-fold compared with VCR solution, respectively. Therefore, these results indicated that HA-NLCs could significantly improve the oral bioavailability and was a promising vehicle for the oral delivery of VCR.
- Mesoporous silica nanoparticles for efficient rivastigmine hydrogen tartrate delivery into SY5Y cells. [Journal Article]
- DDDrug Dev Ind Pharm 2017 Jan 08; :1-9
- Rivastigmine hydrogen tartrate (RT) is a molecule with both hydrophilic and hydrophobic properties used for the treatment of the Alzheimer's disease. In this work, the larger pore size of mesoporous ...
Rivastigmine hydrogen tartrate (RT) is a molecule with both hydrophilic and hydrophobic properties used for the treatment of the Alzheimer's disease. In this work, the larger pore size of mesoporous silica nanoparticles (P1-MSN) was synthesized and then, P1-MSN were functionalized by succinic anhydride (S-P1-MSN) and 3-aminopropyltriethoxysilane (APTES) (AP-CO-P1-MSN) using the grafting and co-condensation methods, respectively. A new method was used for the functionalization of P1-MSN by succinic anhydride at room temperature. Nanoparticles were characterized by special instrumental analysis and loaded by RT. Maximum entrapment efficiency and RT loading percentage into P1-MSN, AP-CO-P1-MSN and S-P1-MSN were respectively obtained as 21.26 and 25.5%, 41.5 and 49.8%, and 11.9 and 14.28% for 24 h. In the simulated gastric and body fluids, the release rate of RT-loaded AP-CO-P1-MSN (AP-CO-P1-MSN-RT) was lower than that of other RT-loaded nanoparticles. In oral pathway, the sustained release of RT was observed in AP-CO-P1-MSN-RT. Moreover, no cytotoxicity effect was observed for P1-MSN, but the cells treated by AP-CO-P1-MSN showed a reduction in SY5Y cell viability due to easy entrance of these nanoparticles and their accumulation in different parts of the cell as observed by TEM.
- Improved oral bioavailability and therapeutic efficacy of dabigatran etexilate via Soluplus(®)-TPGS binary mixed micelles system. [Journal Article]
- DDDrug Dev Ind Pharm 2016 Dec 29; :1-36
- The clinical use of dabigatran etexilate (DABE) is limited by its poor absorption and relatively low bioavailability. Our study aimed to explore the potential of a mixed micelle system composed of So...
The clinical use of dabigatran etexilate (DABE) is limited by its poor absorption and relatively low bioavailability. Our study aimed to explore the potential of a mixed micelle system composed of Soluplus(®) and D-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) to improve the oral absorption and bioavailability of DBAE. DBAE was first encapsulated into Soluplus/TPGS mixed micelles by a simple thin film hydration method. The DBAE loaded micelles displayed an average size distribution of around 83.13 nm. The cellular uptake of DBAE loaded micelles in Caco-2 cell monolayer was significantly enhanced by 2 to 2.6 fold over time as compared with DBAE suspension. Both lipid raft/caveolae and macropinocytosis mediated the cell uptake of DBAE loaded micelles through P-glycoprotein (P-gp)-independent pathway. Compared with the DBAE suspension, the intestinal absorption of DBAE from DBAE mixed micelles in rats was significantly improved by 8 and 5-fold in ileum at 2 h and 4 h, respectively. Moreover, DBAE mixed micelles was absorbed into systemic circulation via both portal vein and lymphatic pathway. The oral bioavailability of DBAE mixed micelles in rats was 3.37 fold higher than that of DBAE suspension. DBAE mixed micelles exhibited a comparable anti-thrombolytic activity with a thrombosis inhibition rate of 63.18% compared with DBAE suspension in vivo. Thus, our study provides a promising drug delivery system to enhance the oral bioavailability and therapeutic efficacy of DBAE.
- The influence of direct compression powder blend transfer method from the container to the tablet press on product critical quality attributes: a case study. [Journal Article]
- DDDrug Dev Ind Pharm 2017 Jan 17; :1-9
- CONCLUSIONS: The results of the study can be of practical relevance to the pharmaceutical industry in the area of direct compression of low-dose formulations, which could be prone to content uniformity (CU) issues.The correct design of blend transfer over single unit processes is an important issue and should be investigated during the development phase since it may influence the final product CQAs. The manual scooping method, although simplistic, can be a temporary solution to improve the results of API's content and uniformity when compared to industrial gravitational transfer.
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- Integrating biopharmaceutics risk assessment and in vivo absorption model in formulation development of BCS class I drug using the QbD approach. [Journal Article]
- DDDrug Dev Ind Pharm 2016 Dec 29; :1-29
- CONCLUSIONS: A simplified scoring system for the biopharmaceutics risk assessment roadmap (BioRAM) is proposed to guide product development.Understanding the clinical implications of the adopted formulation approach led to the construction of purposeful design space and control strategy.