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Colorectal cancer (CRC) is an extremely frequent and fatal disease. The risk of developing CRC is influenced by both environmental and genetic variables, which are covered in this article. The epidemiology of CRC and colorectal screening, as well as the benefits and drawbacks of colonoscopy, are all highlighted. We conducted a narrative review analysis utilizing a comprehensive literature search in MEDLINE/PubMed (using combinations of the following search terms: " colorectal cancer, Colonoscopy, diagnosis, screening, risk factors" " our search was completed in June, 2019. Regular screening can help avoid a variety of colorectal cancers. Screening can detect precancerous polyps, which are abnormal growths in the colon or rectum that can be removed before they develop into cancer. Colorectal cancer is highly treatable when detected early, thus screening is crucial. Colorectal cancer has no symptoms in the early stages, but they arise as the cancer grows. According to the American Cancer Society, colorectal cancer screening should begin around the age of 45. A colonoscopy is the most effective colorectal cancer screening test available. It is the only test that can also prevent a variety of colorectal cancers.

Epilepsy is a chronic and the fourth most common neurological disorder which affects people of all age groups. Recently research and awareness on epilepsy-related deaths have rapidly grown over the past two decades. Many previous studies are attributed to the guidelines that apprise health care professionals in handling these deaths, but there is a relative scarcity of information accessible for clinicians and pharmacists who are responsible for manufacturing or preparing the extemporaneous anti-epileptic suspensions in the hospitals. Mostly in partial seizures, phenytoin is one of the first-choice drugs. In Saudi Arabian hospitals, the extemporaneous preparation of phenytoin suspension is common, but the hot climatic weather in Saudi Arabia possesses stability problems that should be tackled as the prepared suspension should pass all the stability tests to ensure uniform dosage of the extemporaneous formulation. In the current study, the commercial capsules were used to prepare the oral phenytoin sodium extemporaneous suspension. The physical, chemical and microbiological stability of phenytoin sodium suspension is analyzed at various temperatures.

Background Limited information is known about the storage conditions of medicinal products post-dispensing in Saudi Arabia (SA). The particularly hot and humid climate in the region may lead to the loss of essential performance specifications. Objective To investigate the conditions in which medications are held after being dispensed, and up until administration by households in SA. In addition, storage practices adopted by households in the region, as well as their knowledge and awareness are explored. This study also discusses the opportunity of utilising Time-Temperature Indicators (TTIs) in the pharmaceutical industry in SA as a quality-assurance enhancement solution. Methods A cross-sectional questionnaire targeted at households in SA was designed to explore storage practices, background knowledge and awareness of factors that can influence drug stability. Additionally, temperature and relative humidity mapping of 35 different rooms in various homes and cities in SA, as well as car interiors, was performed. Results More than 1000 households have participated in this study from all regions of SA. Approximately, 95% have claimed to take part in storing medications at home. First-aid and supplemental purposes were two of the reasons 80.9% have claimed, while 43.2% claimed treatment for chronic conditions. Just over 35% claimed that not knowing how to dispose of medications, is the reason behind their storage. More than 35% of participants could not identify most suitable storage conditions, and >10% were unaware of the effect storage conditions may have on shelf-life. Many were found to store medication in inappropriate areas, liquid dosage forms for example were stored in freezers by more than 3%. Upon monitoring temperatures of all room types, 25oC was exceeded throughout a 24-hour duration in bathrooms, kitchens and limited use rooms. Temperatures in parked car interiors exceeded 70oC. Conclusions A significant percentage of households in SA lacked knowledge and awareness of good storage practices. However, due to high temperatures observed in the region, increasing knowledge and awareness is not enough, as medicinal cabinets with basic temperature control (e.g. designated secure fridge) are needed. Additionally, the use of TTIs to provide consumers with accumulated thermal history may enhance quality-assurance of thermally sensitive products.

The current study coupled fabric phase sorptive extraction (FPSE) with ultraperformance liquid chromatography method with electrospray ionization and tandem mass detection (UPLC-ESI-MS/MS) for fast and sensitive determination of tadalafil (TAD) in a bioequivalence study. Fabric phase sorptive extraction allowed direct extraction of TAD from the sample matrix with improved selectivity, repeatability, and recoveries. A sol-gel Carbowax 20 M (CX-20 M) coated FPSE membrane revealed the best extraction efficiency for TAD because of its strong affinity for analytes via intermolecular interactions, high mass transfer rate to FPSE membrane, and high permeability. An automated multiple reaction monitoring (MRM) optimizer was employed for the best selection of the precursor and product ions, ion breakdown profile, the fine adjustment of the fragmentor voltages for each precursor ions, and the collision energies for the product ions. The chromatographic separation was conducted using a mobile phase A: 5.0 mM ammonium acetate with 0.1 % formic acid in water and mobile phase B: formic acid (0.1%) in acetonitrile in ratio (55:45, v/v) through isocratic elution mode on an Agilent EclipsePlus C18 (50 × 2.1 mm, 1.8 μm) column and the flow rate was adjusted at 0.4 mL min

Background: Inappropriate disposal practices of medicinal products by households can harm nature. Alternatively, passing unused medications to friends and family members can have undesirable consequences as the quality of the product is in question. Objective: To investigate the disposal and recycling practices of medicinal products by households in Saudi Arabia. Methods: A cross-sectional questionnaire designed to investigate disposal and recycling practices aimed at households in Saudi Arabia. Phone interviews were conducted with healthcare providers from hospitals and community pharmacies as well as medical charity representatives. A thorough search (Jun-September 2020) for disposal and recycling policies was performed on the Saudi Food and Drug Authority (SFDA) and the Ministry of Health websites. Results: More than 900 participants were included in this study. Approximately 40% of respondents claimed to follow the SFDA recommendations for the disposal of unwanted medications in the wastebasket, whilst ≥6% preferred disposal via the toilet. On the other hand, 10% and 5% of households donated their unwanted over-the-counter and prescription-only medication products, respectively, to a person in need, without referring to healthcare professionals. Interviews with healthcare providers and medical charities revealed no drug take-back programs were currently available for households. The SFDA website provides a brief guide on the disposal of unwanted or expired medication. Conclusions: The absence of a clear drug disposal policy for households has created a gap allowing incorrect disposal practices that may lead to harming patients and/or the environment. The launching of drug take-back programs may lead to the provision of a clear consensus of governing bodies and healthcare providers on patient guidance for a safe drug disposal policy.

Purpose: The objective of this work was to formulate a delivery system of pDNA encoded p53 gene-loaded chitosan-sodium deoxycholate (CS-DS) nanoparticles, and to evaluate their influence on in vitro cytotoxicity and transfection efficiency of p53 gene. Methods: The prepared pDNA-loaded CS-DS nanoparticles were evaluated for morphology, particle size, zeta potential, entrapment efficiency %, in vitro release, in vitro cytotoxicity, and transfection efficiency. Results: The mean particle size ranged from from 96.5 ± 11.31 to 405 ± 46.39 nm. All nanoparticles had good positive zeta potential values. Entrapment efficiency % ranged from 38.25 ± 3.25 to 94.89 ± 5.67. The agarose gel electrophoresis confirmed the strong binding between plasmid and CS. The in vitro pDNA release from nanoparticles exhibited an initial burst effect followed by a sustained drug release over a period of 6 days. In vitro cytotoxicity against human Caco-2 cells showed low cell cytotoxicity of plain CS-DS nanoparticles, while pDNA-loaded CS-DS nanoparticles showed a cytotoxic effect with increasing nanoparticles' concentration. Gene transfection, analyzed by PCR and ELISA, showed a direct correlation between gene expression and concentration of pDNA. The highest expression of the gene was achieved with pDNA concentration of 9 µg/mL with 5.7 times increase compared to naked pDNA of the same concentration. Conclusion: The obtained results were very encouraging and offer an alternative approach to enhancing the transfection efficiency of genetic material-loaded chitosan-based delivery systems.

Background and purpose: Conventional topical ophthalmic aqueous solutions and suspensions are often associated with low bioavailability and high administration frequency, pulsatile dose and poor exposure to certain ocular parts. The aim of this study was to develop an ophthalmic nanoparticles loaded gel, for delivering prednisolone acetate (PA), to increase dosing accuracy, bioavailability, and accordingly, efficiency of PA in treating inflammatory ocular diseases. Methods: A novel formulation of self-assembled nanoparticles was prepared by the complexation of chitosan (CS) and, the counter-ion, sodium deoxycholate (SD), loaded with the poorly-water-soluble PA. Particle size, zeta potential, encapsulation efficiency (EE) and drug loading content (LC) of prepared nanoparticles were assessed. Moreover, the nanoparticles were characterized using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). Drug release and eye anti-inflammatory potential of the prepared novel formulation was investigated. Results: Mean particle size of the nanoparticles have dropped from 976 nm ±43 (PDI 1.285) to 480 nm ±28 (PDI 1.396) when the ratio of CS-SD was decreased. The incorporation of 0.1-0.3% of polyvinyl alcohol (PVA), in the preparation stages, resulted in smaller nanoparticles: 462 nm ±19 (PDI 0.942) and 321 nm ±22 (PDI 0.454) respectively. DSC and FTIR results demonstrated the interaction between CS and SD, however, no interactions were detected between PA and CS or SD. Drug release of PA as received, in simulated tears fluid (pH 7.4), showed a twofold increase (reaching an average of 98.6% in 24 hours) when incorporated into an optimized nanoparticle gel formulation (1:5 CS-SD). Conclusion: The anti-inflammatory effect of PA nanoparticles loaded gel on female guinea pig eyes was significantly superior to that of the micronized drug loaded gel (P < 0.05).

Hany SM Ali,1,2 Ahmed F Hanafy,1,3 Abdulmalik Alqurshi1 1Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia; 2Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt; 3Research and Development Department, Al Andalous Pharmaceutical Industries, Cairo, Egypt Introduction: Presenting poorly water-soluble drugs as nanoparticles has shown to be an effective technique in enhancing drug dissolution rate, intrinsic solubility, and thus oral bioavailability. Nevertheless, working with nanoparticles introduces many challenges, one of which is their physical instability. Formulating nanoparticles into a solid dosage form may overcome such challenges and thus unlock the potential benefits of nanosizing. Methods: The current work investigates the possibility of developing a novel solid dosage form, with enhanced dissolution rate, whereby nanocrystals (~400nm) of the class II Biopharmaceutical Classification System drug, glyburide (GBD) were fabricated through combined precipitation and homogenization procedures. Using a novel, but scalable, spraying technique, GBD nanocrystals were loaded onto commonly used tablet fillers, water-soluble lactose monohydrate (LAC), and water insoluble microcrystalline cellulose (MCC). Conventional tableting processes were then used to convert the powders generated into a tablet dosage form. Results: Studies of redispersibility showed considerable preservation of size characteristics of GBD nanocrystals during downstream processing with redispersibility indices of 105 and 118 for GBD–LAC and GBD–MCC, respectively. Characterization by differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy showed that the powders generated powders contained nanosized crystals of GBD which adhered to carrier surfaces. Powder flowability was characterized using Hausner ratio (HR) and Carr’s index (CI). GBD–LAC-loaded particles exhibited poor flowability with CI and HR of 37.5% and 1.60, respectively, whilst GBD–MCC particles showed a slightly improved flowability with CI and HR of 26.47% and 1.36, respectively. The novel tablet dosage form met US Pharmacopeia specifications, including drug content, hardness, and friability. Conclusion: Higher dissolution rates were observed from the nanocrystal-based tablets compared to the microsized and commercial drug formulations. Moreover, the novel nanocrystal tablet dosage forms showed enhanced in vivo performance with area under the plasma concentration–time curve in the first 24 hours values 1.97 and 2.24 times greater than that of marketed tablets. Keywords: glyburide, nanocrystals, downstream, tablet, bioavailability, solidification, redispersibility

Measuring tablet disintegration is essential for quality control purposes; however, no established method adequately accounts for the timeframe or small volumes of the medium associated with the dissipation process for fast disintegrating tablets (FDTs) in the mouth. We hypothesised that digital imaging to measure disintegration in a low volume of the medium might discriminate between different types of FTD formulation. A digital image disintegration analysis (DIDA) was designed to measure tablet disintegration in 0.05–0.7 mL of medium. A temperature-controlled black vessel was 3D-printed to match the dimensions of each tablet under investigation. An overhead camera recorded the mean grey value of the tablet as a measure of the percentage of the formulation which remained intact as a function of time. Imodium Instants, Nurofen Meltlets and a developmental freeze-dried pilocarpine formulation were investigated. The imaging approach proved effective in discriminating the disintegration of different tablets (p < 0.05). For example, 10 s after 0.7 mL of a saliva simulant was applied, 2.0 ± 0.3% of the new pilocarpine tablet remained, whereas at the same time point, 22 ± 9% of the Imodium Instants had not undergone disintegration (temperature within the vessel was 37 ± 0.5°C). Nurofen Meltlets were observed to swell and showed a percentage recovery of 120.7 ± 2.4% and 135.0 ± 6.1% when 0.05 mL and 0.7 mL volumes were used, respectively. Thus, the new digital image disintegration analysis, DIDA, reported here effectively evaluated fast disintegrating tablets and has the potential as a quality control method for such formulations. Supplementary Information The online version contains supplementary material available at 10.1208/s12249-021-02080-0.

Brain-derived neurotrophic factor (BDNF) recognized to be involved in differentiation and proliferation of specialized cell such as osteoblast cell and endothelial cell. The study designed to identify the effect of exogenous BDNF on development of jaw and on neural marker expression. Twenty pregnant rats, ten rats injected (I.M) with 0.1 ml normal saline, other ten injected (I.M) with 0.1 ml of BDNF. Rats were received three doses at intervals (0, 7, 14 day of gestation periods).The developmental jaw of embryos in 16th and 18th intra-uterine life studied for histological and immune-histochemical investigations. The results Illustrated an enhancement of bone development during proceeding embryonic periods for both study groups .Moreover, the experimental group showed a significant differences in the mean of bone cell count at 18th day in comparison to 16th day IUL, and in comparison to control. Results revealed a positive expression of neuronal marker by proliferating nerve cells with a significant difference in comparison between experimental and control. The study suggests that BDNF may contributed in promoting the differentiation of bone cells and enhancement of bone formation with increasing in expression of neuron marker.

The aim of this study was to develop a freeze-dried buccal tablet for the rapid delivery of naloxone in opioid overdose. The tablet composition was optimized to produce an amorphous matrix, which was confirmed by the absence of peaks associated with crystallinity observed by differential scanning calorimetry and powder X-ray diffraction. Tablets with high gelatin content lacked adequate porosity. Mannitol was added to the formulation to bridge and intercalate gelatin's tight polymer aggregates, however sodium bicarbonate was also required to prevent crystallization within the tablets. A linear reduction in mannitol's recrystallization enthalpy was observed with increasing sodium bicarbonate concentration (ΔrecryH = -20.3[NaHCO3] + 220.9; r(2) = 0.9, n = 18). The minimum sodium bicarbonate concentration for full inhibition of mannitol crystallization was 10.9% w/w. Freeze-dried tablets with lower amounts of sodium bicarbonate possessed a crystalline fraction that PXRD identified as mannitol hemihydrate from the unique peak at 9.7° 2θ. Mannitol's greater affinity for both ions and residual water rather than its affinity for self-association was the mechanism for the inhibition of crystallization observed here. The optimized tablet (composition mannitol 24% w/w (4.26 mg), gelatin 65% w/w (11.7 mg), sodium bicarbonate 11% w/w (1.98 mg), and naloxone 800 μg) formed predominantly amorphous tablets that disintegrated in less than 10 s. Optimized tablets were chemically and physically stable over 9 months storage at 25 °C. As speed of drug liberation is the critical performance attribute for a solid dosage form designed to deliver drug in an emergency, a novel imaging based in vitro disintegration assay for buccal tablets was developed. The assay was optimized with regard to conditions in the buccal cavity: i.e., temperature 33-37 °C, volume of medium (0.1-0.7 mL), and use of mucin-containing biorelevant medium. The disintegration assay was sensitive to temperature, medium volume, and medium composition; naloxone tablet disintegration was extremely rapid, with full disintegration ranging from 5 to 20 s. In conclusion, rapidly disintegrating tablets have been developed which are suitable for proof-of-concept clinical trial in humans to determine the pharmacokinetics of naloxone delivered via the buccal route.

Purpose: The objective of this work was to formulate a delivery system of pDNA encoded p53 gene-loaded chitosan-sodium deoxycholate (CS-DS) nanoparticles, and to evaluate their influence on in vitro cytotoxicity and transfection efficiency of p53 gene. Methods: The prepared pDNA-loaded CS-DS nanoparticles were evaluated for morphology, particle size, zeta potential, entrapment efficiency %, in vitro release, in vitro cytotoxicity, and transfection efficiency. Results: The mean particle size ranged from from 96.5 ± 11.31 to 405 ± 46.39 nm. All nanoparticles had good positive zeta potential values. Entrapment efficiency % ranged from 38.25 ± 3.25 to 94.89 ± 5.67. The agarose gel electrophoresis confirmed the strong binding between plasmid and CS. The in vitro pDNA release from nanoparticles exhibited an initial burst effect followed by a sustained drug release over a period of 6 days. In vitro cytotoxicity against human Caco-2 cells showed low cell cytotoxicity of plain CS-DS nanoparticles, while pDNA-loaded CS-DS nanoparticles showed a cytotoxic effect with increasing nanoparticles' concentration. Gene transfection, analyzed by PCR and ELISA, showed a direct correlation between gene expression and concentration of pDNA. The highest expression of the gene was achieved with pDNA concentration of 9 µg/mL with 5.7 times increase compared to naked pDNA of the same concentration. Conclusion: The obtained results were very encouraging and offer an alternative approach to enhancing the transfection efficiency of genetic material-loaded chitosan-based delivery systems.

Melting points for new drugs are reported in regulatory documents, e.g. investigational brochures, and frequently in published research; however, the authors do not typically consider that heat-induced degradation can affect the melting point measurement. Applying a single heating rate is not adequate, and thus many melting points in the literature and regulatory documentation are not valid. Our aim was to validate a five-stage approach for the melting point measurement of heat-sensitive drugs. These stages are; (1) observe melting; (2) record mass loss; (3) measure melting points at different heating rates; (4) characterise degradation and (5) test for potential isomerisation. Applying this approach to pilocarpine HCl illustrated the sensitivity of a melting point to thermal degradation. Due to salt disproportionation & loss of HCl gas, pilocarpine’s melting point decreased by 14 °C when the heating rate was lowered from 20 to 1 °C/min. Epimerization occurred before melting was reached. Increasing the heating rate diminished disproportionation; however, this did not remove epimerization. Thus, the melting point of pilocarpine HCl of 205.5 ± 0.4 °C measured at 20 °C/min represents the melt of a racemic mixture containing inactive isopilocarpine. Heating above the melting point accelerated degradation, a rate of 5 °C/min recovered just 38 ± 1% of pilocarpine. Such data predicted a shelf-life of 6.6 years. Pilocarpine successfully validated the multistage approach by providing new knowledge concerning its thermal stability. Our 5-stage approach must be applied to all new drugs especially if their formulation requires heat. For example, thermal stability is an infrequently considered pre-requisite in the emerging field of 3D printing.

Conversion into the amorphous form enhances the dissolution of poorly soluble drugs, however the barrier to market for medicines containing an amorphous drug is poor stability. The aim was to produce the amorphous form of a drug within a capsule, without thermal or mechanical stress during manufacture. To facilitate this aim, the mechanism for drug-polymer interaction was explored. Nifedipine and polyvinylpyrrolidone were dissolved in tert-butanol at different drug/polymer ratios. These solutions were dispensed into gelatin capsules and freeze-dried. Differential scanning calorimetry (DSC) & novel FT-IR analysis based on peak symmetry measurements confirmed the absence of crystallinity when polyvinylpyrrolidone exceeded 50%w/w. Capsules containing 10 mg of nifedipine were amorphous and stable for over 3 months at ≈40 °C. Evidence of hydrogen bonding between the N-H group of nifedipine and the C=O group of PVP was observed and this interaction inhibited nifedipine crystallisation. PVP’s high affinity for water and the nifedipine-polymer interaction lead to a significant dissolution rate enhancement. The freeze-dried capsule, 10%w/w nifedipine/PVP, had the highest dissolution rate constant of 0.37 ± 0.05 min−1, and the lowest time to achieve 50% dissolution or t1/2 of 1.88 ± 0.05 min. This formulation reached 80% dissolved in less than 6 min whereas the equivalent marketed liquid filled nifedipine capsule took 3 times longer to reach 80% dissolution.

Introduction Deaths from opioid overdose can be prevented through administration of the antagonist naloxone, which has been licensed for injection since the 1970s. To support wider availability of naloxone in community settings, novel non-injectable naloxone formulations are being developed, suitable for emergency use by non-medical personnel. Objectives 1) Identify candidate routes of injection-free naloxone administration potentially suitable for emergency overdose reversal; 2) consider pathways for developing and evaluating novel naloxone formulations. Methods A three-stage analysis of candidate routes of administration was conducted: 1) assessment of all 112 routes of administration identified by FDA against exclusion criteria. 2) Scrutiny of empirical data for identified candidate routes, searching PubMed and WHO International Clinical Trials Registry Platform using search terms “naloxone AND [route of administration]”. 3) Examination of routes for feasibility and against the inclusion criteria. Results Only three routes of administration met inclusion criteria: nasal, sublingual and buccal. Products are currently in development and being studied. Pharmacokinetic data exist only for nasal naloxone, for which product development is more advanced, and one concentrated nasal spray was granted licence in the US in 2015. However, buccal naloxone may also be viable and may have different characteristics. Conclusion After 40 years of injection-based naloxone treatment, non-injectable routes are finally being developed. Nasal naloxone has recently been approved and will soon be field-tested, buccal naloxone holds promise, and it is unclear what sublingual naloxone will contribute. Development and approval of reliable non-injectable formulations will facilitate wider naloxone provision across the community internationally.