Purpose: To develop the osmotically controlled-release gastroprokinetic metoclopramide HCl tablets, using quality by design (QbD)-numerical and graphical optimization technique for the treatment of gastroparesis and prophylaxis of delayed nausea and vomiting induced by low-high emetogenic chemotherapy. Methods: Formulations were designed by central composite design using Design Expert version 11.0.0, with osmogen concentration (X 1), orifice size (X 2), and tablet weight gain after coating (X 3) as input and in-vitro drug release at 1hr. (Y 1), 6 hrs. (Y 2), and 12 hrs. (Y 3), and the regression coefficient of drug release data fitted to zero-order, RSQ zero (Y 4) as output variables. Core tablets prepared by direct compression were coated with Opadry ® CA. The experimental design was validated by the polynomial equation. A correlation between predicted and observed values was evaluated by random checkpoint analysis. The optimized formulations were characterized for drug release, pH effect, osmolarity, agitation intensity, surface morphology, and stability study, and were subjected to accelerated studies according to ICH guidelines. Results: The interaction charts and response surface plots deduced a significant simultaneous effect of X variables on in vitro drug release and RSQ zero. The numerical optimization model predicted >90% drug release with X 1 (13.30%), X 2 (0.6 mm), and X 3 (7.96%). Random checkpoint analysis showed a good correlation between predicted and observed values. The optimized formulation followed zero-order kinetics (r 2 =0.9703) drug release. Shelf life calculated was 2.8 years as per ICH guidelines. Conclusion: The QbD-based approach was found successful in developing controlled release osmotic tablets of metoclopramide HCl, for reducing the dosage frequency, better emetic control, and improve patient compliance.

This study systematically investigated the potential of four model drugs (verapamil HCl, flurbiprofen, atenolol, and furosemide), each belonging to a different class of Biopharmaceutics Classification Systems (BCS) to be developed into oral modified release dosage forms after loading with halloysite nanotubes (HNTs). Methods: The drugs were studied for their loading (mass gain %) by varying solvent system, method, pH, and ratios of loading into the nanotubes using D-optimal split-plot design with the help of Design Expert software. Drug-loaded halloysites were characterized by XRD, DTA, FTIR, SEM, and HPLC-UV-based assay procedures. Dissolution studies were also performed in dissolution media with pH 1.2, 4.5, and 6.8. Moreover, the optimized samples were evaluated under stress stability conditions for determining prospects for the development of oral dosage forms. Results: As confirmed with the results of XRD and DTA, the drugs were found to be converted into amorphous form after loading with halloysite (HNTs). The drugs were loaded in the range of ~7-9% for the four drugs, with agitation providing satisfactory and equivalent loading as compared to vacuum plus agitation based reported methods. FTIR results revealed either only weak electrostatic (verapamil HCl and flurbiprofen) or no interaction with the surface structure of the HNTs. The dissolution profiling depicted significantly retarded release of drugs with Fickian diffusion from a polydisperse system as a model that suits well for the development of oral dosage forms. HPLC-UV-based assay indicated that except furosemide (BCS class IV), the other three drugs are quite suitable for development for oral dosage forms. Conclusion:The four drugs investigated undergo phase transformation with HNTs. While agitation is an optimum method for loading drugs with various physicochemical attributes into HNTs; solvent system, loading ratios and pH play an important role in the loading efficiency respective to the drug properties. The study supports the capability of developing HNT-based modified release oral dosage forms for drugs with high solubility.

ABSTRACT… Introduction: Due to irresponsible and unsafe methods of drug disposal employed by consumers pharmaceutical waste enters the ecosystem, ultimately having a detrimental effect on both human health and environment. Objectives: The purpose of the study is to measure attitude and practice of local community in Karachi, Pakistan regarding safe disposal of unwanted medicines and assess willingness of participants to take part in a medicationtake-back program. Study Design: A two-phase observational study was conducted using convenience sampling. Period: January to February, 2016. Methodology: In Phase I (n = 200) students enrolled in various health sciences institutions in the study were asked to take part in the survey. In Phase II(n = 300) household consumers were contacted by telephone and social media. Results: Participants (response rate 84.4%) were given a questionnaire to explore their attitudes towards medicine disposal. More than half of the consumers surveyed reported storing unused/expired medications in their homes, and majority threw away unwanted medicine in the garbage. The most common reason was unawareness of expiry date (32.7%). Only 12.32% reported returning medication to a pharmacy for disposal. Majority of the consumers had never received advice about medication disposal by a health care provider but were aware of the possible negative consequences and were willing to participate in national pharmacy take-back programs if implemented by the government. Conclusions: Our findings suggest that effective communication and established protocols will promote appropriate disposal practices. Public services in Pakistan, and especially pharmacies, must play a more proactive role in this regard.

Purpose Halloysite nanotubes (HNTs) are a versatile and highly investigated clay mineral due to their natural availability, low cost, strong mechanical strength, biocompatibility, and binding properties. The present work explores its role for retarding and controlling the drug release from the composite polymer matrix material. Methods For this purpose, nanocomposite films comprising propranolol HCl and different concentrations of HNTs were formulated using the “solution casting method”. The menthol in a concentration of 1% w/v was used as a permeation enhancer, and its effect on release and permeation was also determined. Quality characteristics of the nanocomposite were determined, and in vitro release and permeation studies were performed using the Franz diffusion system. The data was analyzed using various mathematical models and permeation parameters. Optimized formulation was also subjected to skin irritation test, FTIR, DSC, and SEM study. Systemic absorption and disposition of propranolol HCl from the nanocomposites were predicted using the GastroPlus TCAT® model. Results The control in drug release rate was associated with the higher concentration of HNTs. F8 released 50% of propranolol within 8 hours (drug, HNTs ratio, 1:2). The optimized formulation (F6) with drug: HNTs (2:1), exhibited drug release 80% in 4 hours, with maximum flux of 145.812 µg/cm 2 hr. The optimized formulation was found to be a non-irritant for skin with a shelf life of 35.46 months (28–30 ℃). The in silico model predicted C max , T max , AUC t , and AUC inf as 32.113 ng/mL, 16.58 h, 942.34 ng/mL×h, and 1102.9 ng/mL×h, respectively. Conclusion The study demonstrated that HNTs could be effectively used as rate controlling agent in matrix type transdermal formulations.

To determine awareness about human papillomavirus (HPV) among female students of medical field in Pakistan. METHODS: A researcher administered, descriptive cross-sectional survey was conducted on a voluntary group of participants (n=629) belonging to medical field from August 2017 to December 2017. After taking permission from the administration random convenient sampling method was adopted. This survey included only female students who were currently studying in departments of medical/health sciences. Students of first and second professionals were excluded because they are beginners in medical fields. RESULTS: The main source of information regarding HPV was academic curriculum (38.25%) of the respondents, with only 21.70% claiming that healthcare providers had educated them about the same. However, 70.11% also reported that HPV/Pap test had never been recommended by their doctors. Many participants 36.09% had no prior knowledge of HPV vaccines; while 56.28% were willing to get vaccinated, the remaining 23.21% claimed a variety of reasons for their unwillingness and rest were uncertain. The top three reasons cited for unwillingness were being sexually inactive 54.79%, the reason of not knowing anything about vaccine 6.84% and cost of vaccines 6.84%. CONCLUSION: This study established that despite having knowledge about HPV, the populace required sufficient information about HPV vaccination for its acceptance and to prevent and combat the disease.