An Advanced Twin-Screw Granulation Technology: The use of Non-Volatile Solvents with High Solubilizing Capacity.

PURPOSE: Twin-screw wet granulation (TSWG) is a manufacturing process that offers several advantages for the processing of water-insoluble active pharmaceutical ingredients (APIs) and has been used for increasing the solubility and dissolution rates. Here we introduce a novel TSWG approach with reduced downstream processing steps by using non-volatile solvents as granulating binders. METHODS: Herein, TSWG was carried out using Transcutol a non-volatile protic solvent as a granulating binder and dissolution enhancer of ibuprofen (IBU) blends with cellulose polymer grades (Pharmacoat® 603, Affinisol™, and AQOAT®). RESULTS: The physicochemical characterisation of the produced granules showed excellent powder flow and the complete transformation of IBU into the amorphous state. Dissolution studies presented immediate release rates for all IBU formulations due to the high drug-polymer miscibility and the Transcutol solubilising capacity. CONCLUSIONS: Overall, the study demonstrated an innovative approach for the development of extruded granules by processing water-insoluble APIs with non-volatile solvents for enhanced dissolution rates at high drug loadings.

Sustained release of 3D printed bupropion hydrochloride tablets bearing Braille imprints for the visually impaired.

3D printing has been introduced as a novel approach for the design of personalized dosage forms and support patient groups with special needs that require additional assistance for enhanced medication adherence. In this study liquid crystal display (LCD) is introduced for the development of sustained release bupropion.HCl printed tablets. The optimization of printing hydrogel inks was combined with the display of Braille patterns on the tablet surface for blind or visually impaired patients. Due to the high printing accuracy, the Braille patterns could be verified by blind patients and provide the required information. Further characterization revealed the presence of BUP in amorphous state within the photopolymerized resins. The selection of poly(ethylene glycol) (PEG)-diacrylate (PEGDA) of different molecular weights and the presence of surfactants or solubilizers disrupted the resin photopolymerization, thus controlling the BUP dissolution rates. A small batch scale-up study demonstrated the capacity of LCD to print rapidly a notable number of tablets within 24 min.

In Vitro Profile of Hydrocortisone Release from Three-Dimensionally Printed Paediatric Mini-Tablets.

Three-dimensional (3D) printing is quickly being adopted in pharmaceutics due to the many advantages it offers, including treatment, adaptability, the reduction in waste and the accelerated development of new formulations. In this study, micro-extrusion printing was implemented for the production of modified-release hydrocortisone (HCT) mini-tablets for paediatric patients. For the developed formulations, Gelucire® 44/14 and Precirol® ATO 5 were used as the main inks at three different ratios: 70%/30%, 60%/40% and 50%/50%, respectively. The printing parameters (temperature and pressure) were altered accordingly for each ratio to achieve printability. The printed mini-tablets exhibited excellent printing quality, featuring consistent layer thicknesses and smooth surfaces. Dissolution tests were performed, and the results indicated a successful modified release of HCT from the mini-tablets. In summary, micro-extrusion exhibited favourable processing abilities for powder blends, facilitating quick printing and the fabrication of potential personalized dosages.

3D-Printed Melatonin Tablets with Braille Motifs for the Visually Impaired.

An innovative approach for creating customized dosage forms and supporting patient populations with specific requirements who need additional support to improve drug adherence is 3D printing. This work introduces liquid crystal display (LCD) 3D printing as a means of developing melatonin (MLT) tablets. For patients who are blind or visually challenged, Braille patterns were displayed on the tablet surface in addition to the optimization of printing hydrogel inks. Owing to the great printing accuracy, blind patients could validate the Braille patterns that provided the required information. Upon further examination MLT was found to be present in the photopolymerized resins in an amorphous state. The choice of poly(ethylene glycol)-diacrylate (PEGDA) with varying molecular weights and the inclusion of surfactants or solubilizers interfered with the photopolymerization of the resin, hence controlling the rates of MLT dissolution towards the sought sustained release. Nuclear magnetic resonance (NMR) analysis showed that photopolymerization of the PEGDA resins in the printed dosage forms has taken place. A small batch scale-up investigation showed that LCDs could print a significant number of tablets quickly-about twenty-four minutes.

Three-Dimensionally Printed Vaginal Rings: Perceptions of Women and Gynecologists in a Cross-Sectional Survey.

Three-dimensional printing technologies can be implemented for the fabrication of personalized vaginal rings (VRs) as an alternative approach to traditional manufacturing. Although several studies have demonstrated the potential of additive manufacturing, there is a lack of knowledge concerning the opinions of patients and clinicians. This study aimed to investigate the perception of women and gynecologists regarding VRs with personalized shapes. The devices were printed with different designs (traditional, "Y", "M", and flat circle) by Fused Deposition Modeling for a cross-sectional survey with 155 participants. Their anticipated opinion was assessed through a questionnaire after a visual/tactile analysis of the VRs. The findings revealed that most women would feel comfortable using some of the 3D-printed VR designs and demonstrated good acceptability for the traditional and two innovative designs. However, women presented multiple preferences when the actual geometry was assessed, which directly related to their age, previous use of the vaginal route, and perception of comfort. In turn, gynecologists favored prescribing traditional and flat circle designs. Overall, although there was a difference in the perception between women and gynecologists, they had a positive opinion of the 3D-printed VRs. Finally, the personalized VRs could lead to an increase in therapeutic adherence, by meeting women's preferences.

Coupling of Fused Deposition Modeling and Inkjet Printing to Produce Drug Loaded 3D Printed Tablets.

In the current study, we have coupled Fused Deposition Modelling (FDM) for the fabrication of plain polyvinyl alcohol (PVA) tablets followed by dispensing of minoxidil ethanolic solutions using inkjet printing. The use of a drop-on-solid printing approach facilitates an accurate and reproducible process while it controls the deposition of the drug amounts. For the purpose of the study, the effect of the solvent was investigated and minoxidil ink solutions of ethanol 70% v/v (P70) or absolute ethanol (P100) were applied on the plain PVA tablets. Physicochemical characterization showed that solvent miscibility with the polymer substrate plays a key role and can lead to the formation of drug crystals on the surface or drug absorption in the polymer matrix. The produced minoxidil tablets showed sustained release profiles or initial bursts strongly affected by the solvent grade used for dispensing the required dose on drug loaded 3D printed tablets. This paradigm demonstrates that the coupling of FDM and inkjet printing technologies could be used for rapid development of personalized dosage forms.

Prevalence of psoriatic arthritis among patients with plaque psoriasis: a Brazilian retrospective study.

BACKGROUND: Psoriatic arthritis is the most frequent and impactful comorbidity among psoriatic patients and appears in most cases after skin disease. Dermatologists play a key role in its early diagnosis and treatment. OBJECTIVE: To determine the prevalence of psoriatic arthritis and associated variables among patients with plaque psoriasis seen at a reference center for treating psoriasis. DESIGN AND SETTING: Retrospective cross-sectional study conducted among 300 patients at an outpatient clinic in a university center in Juiz de Fora, MG, Brazil. METHODS: Standardized records of 300 patients with plaque psoriasis were examined. Demographic data and medical variables relating to psoriasis (Psoriasis Area and Severity Index (PASI), family history, age at onset and disease progression) and psoriasis arthritis (CASPAR criteria) were evaluated. Laboratory and radiographic tests in the medical records were reviewed. RESULTS: Seventy-three (24.3%) of these 300 patients with plaque psoriasis had psoriatic arthritis. Asymmetric oligoarthritis (58.9%) was the most common clinical form, followed by polyarthritis (20.5%), distal interphalangeal arthritis (15.2%) and spondyloarthritis (5.4%). Dactylitis was present in 21.9% and enthesitis in 35.6% of patients. Compared with patients without arthritis, patients with arthritis had higher average age, higher frequency of positive family history of psoriasis, longer duration of evolution and higher PASI rates. CONCLUSION: Psoriatic arthritis is often underdiagnosed. Since dermatologists perform the initial approach, these professionals need to be trained to diagnose this comorbidity and treat it, together with rheumatologists.

Prevalence of psoriatic arthritis among patients with plaque psoriasis: a Brazilian retrospective study

ABSTRACT BACKGROUND: Psoriatic arthritis is the most frequent and impactful comorbidity among psoriatic patients and appears in most cases after skin disease. Dermatologists play a key role in its early diagnosis and treatment. OBJECTIVE: To determine the prevalence of psoriatic arthritis and associated variables among patients with plaque psoriasis seen at a reference center for treating psoriasis. DESIGN AND SETTING: Retrospective cross-sectional study conducted among 300 patients at an outpatient clinic in a university center in Juiz de Fora, MG, Brazil. METHODS: Standardized records of 300 patients with plaque psoriasis were examined. Demographic data and medical variables relating to psoriasis (Psoriasis Area and Severity Index (PASI), family history, age at onset and disease progression) and psoriasis arthritis (CASPAR criteria) were evaluated. Laboratory and radiographic tests in the medical records were reviewed. RESULTS: Seventy-three (24.3%) of these 300 patients with plaque psoriasis had psoriatic arthritis. Asymmetric oligoarthritis (58.9%) was the most common clinical form, followed by polyarthritis (20.5%), distal interphalangeal arthritis (15.2%) and spondyloarthritis (5.4%). Dactylitis was present in 21.9% and enthesitis in 35.6% of patients. Compared with patients without arthritis, patients with arthritis had higher average age, higher frequency of positive family history of psoriasis, longer duration of evolution and higher PASI rates. CONCLUSION: Psoriatic arthritis is often underdiagnosed. Since dermatologists perform the initial approach, these professionals need to be trained to diagnose this comorbidity and treat it, together with rheumatologists.