Effects of antiseptic irrigation solutions on osseointegration in a cementless tibial implantation mouse model.

Despite the success of standard antiseptic irrigation solutions in reducing periprosthetic joint infection (PJI) rates, there is still a need for more effective solutions. Synergistic use of povidone-iodine (PI) and hydrogen peroxide (H2O2) has shown promising results; however, the optimal solution concentration balancing bactericidal activity and osseointegration remains unknown. This study aims to evaluate the impact of these antiseptic irrigation solutions on osseointegration and the bone-implant interface strength in vivo. Forty C57BL/6 mice underwent bilateral tibial implantation surgery and were randomly allocated into three groups receiving 0.3% PI, 10% PI mixed with 3% H2O2, or saline as irrigation solutions intraoperatively. Assessments were performed on postoperative Days 1 and 28, including plain radiographs, microcomputed tomography (microCT) evaluation, histological analysis, immunohistochemistry, and biomechanical pull-out testing. No wound complications were observed. MicroCT scans revealed no differences in peri-implant trabecular bone parameters. Biomechanical pull-out testing showed no differences in the bone-implant interface strength across groups. Histological analysis indicated no differences in bone and bone marrow percentage areas among treatment groups. Immunohistochemical analysis demonstrated no differences among groups in peri-implant osteocalcin, osterix, or endomucin-positive cells. In conclusion, using either antiseptic irrigation solution showed no differences in osseointegration parameters compared to the control group, demonstrating safety and the absence of toxicity. CLINICAL RELEVANCE: Dilute 0.3% povidone-iodine and a 1:1 combination of 10% povidone-iodine mixed with 3% hydrogen peroxide can be safely used during primary and revision total joint arthroplasty without compromising osseointegration or causing wound complications.

Prevention and treatment of peri-implant fibrosis by functionally inhibiting skeletal cells expressing the leptin receptor.

The cellular and molecular mediators of peri-implant fibrosis-a most common reason for implant failure and for surgical revision after the replacement of a prosthetic joint-remain unclear. Here we show that peri-implant fibrotic tissue in mice and humans is largely composed of a specific population of skeletal cells expressing the leptin receptor (LEPR) and that these cells are necessary and sufficient to generate and maintain peri-implant fibrotic tissue. In a mouse model of tibial implantation and osseointegration that mimics partial knee arthroplasty, genetic ablation of LEPR+ cells prevented peri-implant fibrosis and the implantation of LEPR+ cells from peri-implant fibrotic tissue was sufficient to induce fibrosis in secondary hosts. Conditional deletion of the adhesion G-protein-coupled receptor F5 (ADGRF5) in LEPR+ cells attenuated peri-implant fibrosis while augmenting peri-implant bone formation, and ADGRF5 inhibition by the intra-articular or systemic administration of neutralizing anti-ADGRF5 in the mice prevented and reversed peri-implant fibrosis. Pharmaceutical agents that inhibit the ADGRF5 pathway in LEPR+ cells may be used to prevent and treat peri-implant fibrosis.

A model for enterprise resource planning implementation in the Saudi public sector organizations.

Studies dedicated to user's adoption, acceptance, and use of IT have been rampant since the advent of computers and IT. Therefore, it becomes essential to assess the value of IT to organizations and to understand the determinants of such value in terms of acceptance, integration, and technology use. In this regard, Enterprise Resource Planning (ERP) adoption remains challenging for professionals and practitioners alike. Previous research neglected many vital factors, such as user involvement (participation, engagement, and resilience) and environmental factors (change management, competitiveness, and pandemic pressure). Therefore, this study aims to identify the most significant factors that influence the successful adoption of ERP and propose a conceptual model. The Technology Acceptance Model with DeLone and McLean Information Success Models were the base for the study. The findings of this study reveal a conceptual model that facilitates the successful adoption of ERP systems. Through the identification of critical factors, one factor emerged as a permanent component in the adoption process. This conceptual model provides valuable insights for organizations seeking to implement and adopt ERP systems effectively. The study's findings offer valuable insights for firms pursuing long-term economic success through ERP adoption. Understanding the influencing factors enables efficient and effective deployment. Implications are relevant to organizations, ERP vendors, and decision-makers, guiding informed decision-making and prioritizing success factors.

Exploring the feasibility of evaluating a community alliance welfare advice programme co-located in primary care in Bradford: an uncontrolled before and after study.

BACKGROUND: Welfare advice services co-located in health settings are known to improve financial security. However, little is known on how to effectively evaluate these services. This study aims to explore the feasibility of evaluating a welfare advice service co-located in a primary care setting in a deprived and ethnically diverse population. It seeks to investigate whether the proposed evaluation tools and processes are acceptable and feasible to implement and whether they are able to detect any evidence of promise for this intervention on the mental health, wellbeing and financial security of participants. METHODS: An uncontrolled before and after study design was utilised. Data on mental health, wellbeing, quality of life and financial outcomes were collected at baseline prior to receiving welfare advice and at three months follow-up. Multiple logistic and linear regression models were used to explore individual differences in self-reported financial security and changes to mental health, wellbeing and quality of life scores before and after the provision of welfare advice. RESULTS: Overall, the majority of key outcome measures were well completed, indicating participant acceptability of the mental health, wellbeing, quality of life and financial outcome measures used in this population. There was evidence suggestive of an improvement in participant financial security and evidence of promise for improvements in measured wellbeing and health-related quality of life for participants accessing services in a highly ethnically diverse population. Overall, the VCS Alliance welfare advice programme generated a total of £21,823.05 for all participants, with participants gaining an average of £389.70 per participant for participants with complete financial outcome data. CONCLUSIONS: This research demonstrates the feasibility of evaluating a welfare advice service co-located in primary care in a deprived and ethnically diverse setting utilising the ascribed mental health, wellbeing and quality of life and financial outcome tools. It provides evidence of promise to support the hypothesis that the implementation of a welfare advice service co-located in a health setting can improve health and wellbeing and reduce health inequalities.

A vertebral skeletal stem cell lineage driving metastasis.

Vertebral bone is subject to a distinct set of disease processes from long bones, including a much higher rate of solid tumour metastases1-4. The basis for this distinct biology of vertebral bone has so far remained unknown. Here we identify a vertebral skeletal stem cell (vSSC) that co-expresses ZIC1 and PAX1 together with additional cell surface markers. vSSCs display formal evidence of stemness, including self-renewal, label retention and sitting at the apex of their differentiation hierarchy. vSSCs are physiologic mediators of vertebral bone formation, as genetic blockade of the ability of vSSCs to generate osteoblasts results in defects in the vertebral neural arch and body. Human counterparts of vSSCs can be identified in vertebral endplate specimens and display a conserved differentiation hierarchy and stemness features. Multiple lines of evidence indicate that vSSCs contribute to the high rates of vertebral metastatic tropism observed in breast cancer, owing in part to increased secretion of the novel metastatic trophic factor MFGE8. Together, our results indicate that vSSCs are distinct from other skeletal stem cells and mediate the unique physiology and pathology of vertebrae, including contributing to the high rate of vertebral metastasis.

Incidence of silent venous thromboembolism after total hip arthroplasty: A comparison of rivaroxaban and enoxaparin.

PROPOSE: Total hip arthroplasty (THA) is associated with a significant risk of venous thromboembolism (VTE). Different thromboprophylaxis strategies have been used to prevent VTE. The primary aim of this study was to report the incidence of VTE and compare the efficacy and safety of rivaroxaban to enoxaparin. The secondary outcome was to report the incidence of silent deep venous thrombosis (DVT) using computed tomography venography. METHODS: One hundred sixty patients who underwent THA were enrolled in a prospective study. Patients were randomized into two groups as follows: those who received rivaroxaban 10 mg oral daily (group RXE) and those who received enoxaparin 40 IU/day subcutaneously for 14 days (group ENO). RESULTS: Both groups were matched for age, sex, comorbidities, special habits and preoperative laboratory investigations. The overall incidence of DVT was 5% (n = 8), which included four patients clinically diagnosed as having DVT and four with silent DVT. All the DVT cases occurred in veins below the knee and in the group RXE; none of the cases occurred in group ENO (p = 0.04). The incidence of DVT was significantly higher in patients with high body mass indexes (p < 0.001), older age (p = 0.024) and medical comorbidities (p = 0.14). No mortality, pulmonary embolism, stroke, wound infection or major bleeding occurred in either group. CONCLUSIONS: Among the patients who underwent hip arthroplasty, rivaroxaban prophylaxis was found to be associated with lower efficacy and similar safety outcomes as compared with enoxaparin anticoagulants.

Short-term results of triathlon cementless versus cemented primary total knee arthroplasty.

BACKGROUND: Recent studies have demonstrated that aseptic loosening remains a leading cause of failure after total knee arthroplasty (TKA). Cementless fixation is a possible strategy for countering this problem. This study compared short-term survivorship and functional results of patients undergoing primary TKA with cementless versus cemented implants. METHODS: A multi-center database was utilized to identify 3849 patients undergoing primary TKA between 2012 and 2017 with a minimum two-year follow-up. Patients were divided into cementless (699), and cemented TKA (3150). The outcome of TKA including revision for aseptic or septic reasons, and other outcome variables were compared. Six hundred five patients from the cementless group (case) were matched with 605 patients from the cemented group (controls). Both groups were compared for outcomes and related variables. RESULTS: Both matched groups were similar in age, race, gender, height, weight, BMI, laterality, femoral component type, follow-up duration, preoperative and postoperative physical and mental health, and functional activities (all p-values>0.05). Although the cementless TKA group had more components in varus alignment (p = 0.015) and were taller (p < 0.001), the aseptic revision rate and time to failure were similar in both groups (p-values = 0.256 and 0.0890 respectively). The rate of revision for infection was also the same in both groups (p = 0.452). CONCLUSION: Cementless TKA demonstrated an equivalent rate of aseptic and septic failure when compared to cemented TKA in the short-term. Time to aseptic failure was also similar in both groups.

Erroneous introduction of femoral venous catheter into a broad ligament varicose vein causing hemoperitoneum in a woman with postpartum thrombotic microangiopathy.

Femoral venous catheterization is a common procedure in critical care patients. Pregnant women and those in the postpartum period are at risk of various complications such as shock, acute kidney injury, and thrombotic microangiopathic syndromes requiring hemodialysis and plasma exchange, which may necessitate central venous catheterization. Femoral vein catheters may also sometimes be needed. These women may have underlying pelvic congestion and varicosities. Here we present a 24-year-old female patient, who has been treated for postpartum thrombotic microangiopathy with initial clinical improvements, became hemodynamically unstable with diffuse abdominal tenderness and a significant drop in the hemoglobin/hematocrit. Her abdominal ultrasound showed fluid in the peritoneal cavity with hemorrhagic diagnostic tap. The patient underwent exploratory laparotomy which unexpectedly revealed an erroneously introduced femoral vein catheter into a broad ligament varicose vein causing hemoperitoneum and evident ovarian injury. Puncturing of broad ligament varicosities causing hemoperitoneum in peripartum women has not been previously reported as a complication of femoral vein catheterization. This indicates that femoral catheterization in pregnant and peripartum women should be cautiously done and that development of acute abdominal issues, following insertion of femoral vein catheter should raise clinical suspicion and warrant evaluation of catheter misplacement.

Symptomatic Benign Prostatic Hyperplasia: A Risk Factor for Periprosthetic Joint Infection in Male Patients.

BACKGROUND: Male patients undergoing total joint arthroplasty have a higher risk of periprosthetic joint infection (PJI) compared with female patients. The exact reason for this finding is not well known. This study aimed to determine if patients with symptomatic benign prostatic hyperplasia (BPH) are at increased risk of PJI. METHODS: A total of 12,902 male patients who underwent primary or revision total joint arthroplasty from January 2006 to April 2017 were retrospectively identified. The mean patient age was 62.47 years and the mean patient body mass index was 30.1 kg/m. The majority of patients were Caucasian or African American. Most surgical procedures involved the hip joints (57.8%) and were primary arthroplasties (86%). Of these patients, 386 (3%) had symptomatic BPH. Among this group, 250 patients with symptomatic BPH were identified and were matched in an approximate 1:3 ratio with 708 control patients. Using the International Consensus Meeting criteria, patients who developed PJI were identified. RESULTS: The PJI rate was 7.9% in the symptomatic BPH group and 2.8% in the control group. Multivariate regression analysis in unmatched groups showed that symptomatic BPH was a strong independent risk factor for PJI. After matching for variables related to outcomes, symptomatic BPH remained a significant risk factor for PJI (p = 0.01). CONCLUSIONS: Patients with symptomatic BPH had a higher risk of PJI compared with the control patients. This may partly explain the higher rate of PJI that is seen in male patients. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Destructive Osteonecrosis of the Femoral Head After a Single Intra-Articular Corticosteroid Injection: A Report of Two Cases.

INTRODUCTION: Accelerated femoral head avascular necrosis after a single dose intra-articular steroid injection is a rare pathology. Few cases were reported in the literature. Most cases were managed with total hip arthroplasty. CASE PRESENTATION: In this study, we report two rare cases of destructive osteonecrosis of the femoral head. Both patients presented with hip osteoarthritis that failed nonoperative measures. A single intra-articular corticosteroid injection was administered for each patient. Both patients had femoral head destruction and significant resorption at 14 and 11 weeks, respectively. Septic arthritis was ruled out by blood tests and joint aspiration. Total hip arthroplasty (THA) was undertaken and histology reports confirmed the osteonecrosis. The postoperative follow-up was uneventful with satisfactory hip function. DISCUSSION AND CONCLUSION: Destructive osteonecrosis of the femoral head is a rare catastrophic potential complication of intra-articular corticosteroid injection. Hence, physicians must consider this complication when counseling patients before an intra-articular corticosteroid hip injection.

Tranexamic Acid Is Associated With Reduced Periprosthetic Joint Infection After Primary Total Joint Arthroplasty.

BACKGROUND: Previous studies have demonstrated preoperative anemia to be a strong risk factor for periprosthetic joint infection (PJI) in total joint arthroplasty (TJA). Allogeneic blood transfusion can be associated with increased risk of PJI after primary and revision TJA. Tranexamic acid (TXA) is known to reduce blood loss and the need for allogeneic blood transfusion after TJA. The hypothesis of this study is that administration of intravenous TXA would result in a reduction in PJI after TJA. METHODS: An institutional database was utilized to identify 6340 patients undergoing primary TJA between January 1, 2013 and June 31, 2017 with a minimum of 1-year follow-up. Patients were divided into 2 groups based on whether they received intravenous TXA prior to TJA or not. Patients who developed PJI were identified. All PJI patients met the 2018 International Consensus Meeting definition for PJI. A multivariate regression analysis was performed to identify variables independently associated with PJI. RESULTS: Of the patients included, 3683 (58.1%) received TXA and 2657 (41.9%) did not. The overall incidence of preoperative anemia was 16%, postoperative blood transfusion 1.8%, and PJI 2.4%. Bivariate analysis showed that patients who received TXA were significantly at lower odds of infection. After adjusting for all confounding variables, multivariate regression analysis showed that TXA is associated with reduced PJI after primary TJA. CONCLUSION: TXA can help reduce the rate of PJI after primary TJA. This protective effect is likely interlinked to reduction in blood loss, lower need for allogeneic blood transfusion, and issues related to immunomodulation associated with blood transfusion.

Ink-Jet Printed CMOS Electronics from Oxide Semiconductors.

Complementary metal oxide semiconductor (CMOS) technology with high transconductance and signal gain is mandatory for practicable digital/analog logic electronics. However, high performance all-oxide CMOS logics are scarcely reported in the literature; specifically, not at all for solution-processed/printed transistors. As a major step toward solution-processed all-oxide electronics, here it is shown that using a highly efficient electrolyte-gating approach one can obtain printed and low-voltage operated oxide CMOS logics with high signal gain (≈21 at a supply voltage of only 1.5 V) and low static power dissipation.

Post-appendectomy surgical site infection rate after using an antimicrobial film incise drape: a prospective study.

BACKGROUND: An appendectomy is a contaminated or potentially dirty surgical procedure that can be associated with surgical site infection (SSI). METHODS: A single-center unblinded prospective cohort study examined the role of antimicrobial incise film drapes in lowering the rate of SSI after appendectomy. Any patient aged 12 years or older who was scheduled for open appendectomy for acute appendicitis was included. Patients were assigned to two groups. Group 1 (n=52) had the standard five-minute skin preparation with 10% povidone-iodine soap followed by the application of an antimicrobial film incise drape, and group 2 (n=39) had the standard skin preparation alone. RESULTS: Six (11.5%) of the 52 patients who had the antimicrobial film incise drape and two (5.1%) of the 39 patients who did not have the drape developed SSI (p=NS). Of the six patients in the antimicrobial film group with post-operative SSI, three had a perforated appendix, two had a gangrenous appendix, and one had an inflamed appendix. In group 2, one patient had an inflamed appendix and the other had a perforated appendix. The median length of stay in the hospital was two days (range 1-11 days) for both groups. CONCLUSION: Our study did not support the view that antimicrobial film incise drapes can lower the rate of post-appendectomy SSI. Moreover, the length of stay was not minimized by the use of these drapes.

Novel jojoba oil-based emulsion gel formulations for clotrimazole delivery.

Jojoba oil-based emulgel formulations were prepared using different concentrations of various gelling agents, such as hydroxypropyl methylcellulose (HPMC) and Carbopol 934 P and combination of both. The prepared emulgels were physically evaluated for their stability after temperature cycle test, centrifugation and long-term shelf storage for 1 year at room temperature. The in vitro release at 37 °C was studied to define the effect of the concentration and type of the gelling agent. A comparison between the formulated emulgels and two commercially available products, Candistan® and Canesten® creams, was carried out to judge their efficacy and stability. The prepared emulgels exhibited non-Newtonian shear thinning behavior with little or no thixotropy. Four emulgels showed excellent stability as they demonstrated consistent rheological model under different treatment conditions. The in vitro release test showed variation in the extent of percent drug released. The drug release from the commercial preparation was lower than some of the prepared emulgel formulae. One formula containing combination of the two gelling agents (HPMC and Carbopol 934 P), showed excellent stability and high extent of clotrimazole release was microbiologically evaluated against Candida albicans using cylinder and plate method. The selected formula showed superior antimycotic activity compared to the commercially available formulation. Further in vivo animal studies for the obtained stable formula is recommended.

QbD approach of rapid disintegrating tablets incorporating indomethacin solid dispersion.

The development of rapid disintegrating tablets (RDT) requires the use of highly soluble components to support the intended use of these products. In an attempt to prepare RDT of indomethacin, its solid dispersion with polyvinyl pyrrolidone K25 (PVP) was incorporated in a fast disintegrating matrix. Drug polymer interactions were investigated using X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Indomethacin 1:1 solid dispersion with PVP was used to prepare its RDT. Two factors at 3 levels full factorial design were employed as a statistical approach to optimize the amount of superdisintegrant (Ac-di-sol) and hardness value regarding the desired disintegration and release characteristics. Drug to carrier ratio was the controlling factor for dissolution improvement. XRD and FTIR data revealed a remarkable interaction between the drug and the carrier that might be responsible for the dissolution enhancement. Multiple regression analysis revealed a significant effect of the polynomial terms for obtaining rapid disintegrating tablets. It was inferred that the hardness value is the most important factor controlling the disintegration time and the release characteristics. In conclusion, this study demonstrated that quality by design (QbD) is a potential paradigm for understanding the quality and optimizing the formulation of RDT containing indomethacin solid dispersion.

Optimized formulation for topical administration of clotrimazole using Pemulen polymeric emulsifier.

BACKGROUND: Emulgel topical formulation is a vehicle of potential for topical delivery of antifungal drugs. METHODS: The imidazole derivative antifungal drug, clotrimazole (CZ), was formulated into emulgels using two grades of hydrophobically modified co-polymers of acrylic acid, namely Pemulen TR1 and TR2. The prepared emulgels were evaluated for their rheological properties, short- and long-term stability, in vitro release at 37°C. Microbiological evaluation of the formula showed that optimum stability and release was carried out to measure its antifungal activity. RESULTS: All formulae showed non-Newtonian shear thinning behavior with little thixotropy or antithixotropy. Five of the prepared formulae showed good physical stability under different treatment conditions. Isopropyl myristate (IPM) emulgels exhibited higher rate of CZ release than either jojoba oil (JB) or liquid paraffin-based emulgels. A selected formula containing JB together with a combination of Pemulen TR1 and TR2 showed excellent stability as well as high rate of CZ release. Microbiological evaluation of the selected formula containing similar amount of CZ revealed 1.2-folds increase in the antifungal activity compared to commercially available formulation. CONCLUSION: Emulgel dosage form based on Pemulen polymeric emulsifier and JB is a promising vehicle for topical delivery of CZ and further in vivo animal studies are recommended.

Frequency of peripheral arterial disease in patients presenting with acute coronary syndrome at a tertiary care centre in Karachi.

OBJECTIVE: To determine the frequency of symptomatic and asymptomatic peripheral arterial disease (PAD) in patients presenting with acute coronary syndrome (ACS) at a tertiary care center in Karachi. METHODS: A total of 350 consecutive patients presenting with ACS were recruited in this cross-sectional study. All patients were enrolled from the emergency department of the National Institute of Cardiovascular Diseases (NICVD), Karachi. RESULTS: PAD, determined by presence of claudicant symptoms on interview and/or an ankle-brachial index (ABI) score less than 0.90, was present in 17.7% of patients, of whom 9.1% had no symptoms of intermittent claudication (IC) and 11.7% had no rest pain. CONCLUSIONS: Concomitant PAD is frequent among ACS patients in our study. ABI screening is simple and yields a high proportion of patients with extensive atherosclerosis who may require more aggressive atherosclerosis risk management.

Knowledge and awareness about diabetes and periodontal health among Jordanians.

The aim of this study is to evaluate the awareness, perception, sources of information, and knowledge of diabetes mellitus and periodontal health among Jordanians, to examine the factors related to their knowledge, and organize effective education programs. A random sample of 500 diabetic patients was recruited from three hospitals and three comprehensive health centers that represent both urban and rural populations in Jordan between September 25, 2006, and February 20, 2007. Completed questionnaires with the answers were returned by 405 participants (response rate was 81%). Only 28% indicated that they followed up gum diseases with the dentist; 48% were aware that diabetic patients are more prone to gum diseases and oral health complications. About a third (38%) recognized that their periodontal health might affect their glycaemic level. Television and Internet were the main source of knowledge for dentists with the rate of 50%. Knowledge about diabetes and periodontal health among diabetic patients is low, and majority of patients were unaware of the oral health complications of their disease and the need for proper preventive care. Issues on education need to be addressed. Therefore, appropriate educational programs should be planned according to community needs, and the target of these programs should be patients with irregular visits to the dentist and physicians. The clinical implication of our findings is that dentists, physicians, and other health providers should inspect diabetic patients for gum diseases each time they come for care and recommend that diabetic patient see a dentist regularly.

Effect of some formulation parameters on flurbiprofen encapsulation and release rates of niosomes prepared from proniosomes.

Proniosomal gels or solutions of flurbiprofen were developed based on span 20 (Sp 20), span 40 (Sp 40), span 60 (Sp 60), and span 80 (Sp 80) without and with cholesterol. Nonionic surfactant vesicles (niosomes) formed immediately upon hydrating proniosomal formulae. The entrapment efficiency (EE%) of flurbiprofen (a poorly soluble drug) was either determined by exhaustive dialysis of freshly prepared niosomes or centrifugation of freeze-thawed vesicles. The influence of different processing and formulation variables such as surfactant chain length, cholesterol content, drug concentration, total lipid concentration, negatively or positively charging lipids, and the pH of the dispersion medium on flurbiprofen EE% was demonstrated. Also, the release of the prepared niosomes in phosphate buffer (pH 7.4) was illustrated. Results indicated that the EE% followed the trend Sp 60 (C(18))>Sp 40 (C(16))>Sp 20 (C(12))>Sp 80 (C(18)). Cholesterol increased or decreased the EE% depending on either the type of the surfactant or its concentration within the formulae. The maximum loading efficiency was 94.61% when the hydrating medium was adjusted to pH 5.5. Increasing total lipid or drug concentration also increased the EE% of flurbiprofen into niosomes. However, incorporation of either dicetyl phosphate (DCP) which induces negative charge or stearyl amine (SA) which induces positive charge decreased the EE% of flurbiprofen into niosomal vesicles. Finally, in vitro release data for niosomes of Sp 40 and Sp 60 showed that the release profiles of flurbiprofen from niosomes of different cholesterol contents is an apparently biphasic release process. As a result, this study suggested the potential of proniosomes as stable precursors for the immediate preparation of niosomal carrier systems.

Quality by design: understanding the formulation variables of a cyclosporine A self-nanoemulsified drug delivery systems by Box-Behnken design and desirability function.

Quality by design (QBD) refers to the achievement of certain predictable quality with desired and predetermined specifications. A very useful component of the QBD is the understanding of factors and their interaction effects by a desired set of experiments. The present project deals with a case study to understand the effect of formulation variables of nanoemulsified particles of a model drug, cyclosporine A (CyA). A three-factor, three-level design of experiment (DOE) with response surface methodology (RSM) was run to evaluate the main and interaction effect of several independent formulation variables that included amounts of Emulphor El-620 (X(1)), Capmul MCM-C8 (X(2)) and 20% (w/w) CyA in sweet orange oil (X(3)). The dependent variables included nanodroplets size (Y(1)), nanoemulsions turbidity (Y(2)), amounts released after 5 and 10min (Y(3), Y(4)), emulsification rate (Y(5)) and lag time (Y(6)). A desirability function was used to minimize lag time and to maximize the other dependent variables. A mathematical relationship, Y(5)=9.09-0.37X(1)+0.37X(2)-0.45X(3)+0.732X(1)X(2)-0.62X(1)X(3)+0.3X(2)X(3)+0.02X(1)(2)-0.28X(2)(2)+0.471X(3)(2) (r(2)=0.92), was obtained to explain the effect of all factors and their colinearities on the emulsification rate. The optimized nanodroplets were predicted to yield Y(1), Y(2), Y(3), Y(4), Y(5) and Y(6) values of 42.1nm, 50.6NTU, 56.7, 107.2, 9.3%/min and 3.5min, respectively, when X(1), X(2), and X(3) values were 36.4, 70 and 10mg, respectively. A new batch was prepared with these levels of the independent variables to yield Y(1)-Y(6) values that were remarkably close to the predicted values. In conclusion, this investigation demonstrated the potential of QBD in understanding the effect of the formulation variables on the quality of CyA self-nanoemulsified formulations.