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  1. Shah SA, Sohail M, Minhas MU, Nisar-Ur-Rehman, Khan S, Hussain Z, et al.
    Drug Deliv Transl Res, 2019 Apr;9(2):555-577.
    PMID: 29450805 DOI: 10.1007/s13346-018-0486-8
    Cellulose acetate phthalate-based pH-responsive hydrogel was synthesized for fabrication of polymeric matrix tablets for gastro-protective delivery of loxoprofen sodium. Cellulose acetate phthalate (CAP) was cross-linked with methacrylic acid (MAA) using free radical polymerization technique. Fourier transform infrared (FTIR) spectra confirmed the formation of cross-linked structure of CAP-co-poly(methacrylic acid). Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) confirmed the thermal stability of polymeric networks, and scanning electron microscopy (SEM) and energy-dispersive X-ray spectrum (EDS) images unveiled that the prepared formulations were porous in nature and thus the developed formulations had shown better diffusibility. Swelling and in vitro drug release was performed at various pHs and maximum swelling and release was obtained at pH 7.4, while swelling and release rate was very low at pH 1.2 which confirmed the pH-responsive behavior of CAP-co-poly(MAA). CAP-co-poly(MAA) copolymer prevents the release of loxoprofen sodium into the stomach due to reduced swelling at gastric pH while showing significant swelling and drug release in the colon. Cytotoxicity studies revealed higher biocompatibility of fabricated hydrogel. Acute oral toxicity studies were performed for the evaluation and preliminary screening of safety profile of the developed hydrogels. Matrix tablets were evaluated for release behavior at simulated body pH. The investigations performed for analysis of hydrogels and fabricated matrix tablets indicated the controlled drug release and gastro-protective drug delivery of CAP-co-poly(MAA) hydrogels and pH-sensitive matrix tablets for targeted delivery of gastro-sensitive/irritative agents. Graphical abstract.
    Matched MeSH terms: Delayed-Action Preparations/administration & dosage
  2. Singh GK, Turner L, Desai R, Jimenez M, Handelsman DJ
    J Clin Endocrinol Metab, 2014 Jul;99(7):2592-8.
    PMID: 24684468 DOI: 10.1210/jc.2014-1243
    Testosterone (T) and nandrolone (N) esters require deep im injections by medical personnel but these often deposit injectate into sc fat so that more convenient sc self-administration may be feasible.
    Matched MeSH terms: Delayed-Action Preparations/administration & dosage
  3. Lim HP, Tey BT, Chan ES
    J Control Release, 2014 Jul 28;186:11-21.
    PMID: 24816070 DOI: 10.1016/j.jconrel.2014.04.042
    Natural biopolymers have attracted considerable interest for the development of delivery systems for protein drugs owing to their biocompatibility, non-toxicity, renewability and mild processing conditions. This paper offers an overview of the current status and future perspectives of particle designs using biopolymers for the stabilization and controlled-delivery of a model protein drug--insulin. We first describe the design criteria for polymeric encapsulation and subsequently classify the basic principles of particle fabrication as well as the existing particle designs for oral insulin encapsulation. The performances of these existing particle designs in terms of insulin stability and in vitro release behavior in acidic and alkaline media, as well as their in vivo performance are compared and reviewed. This review forms the basis for future works on the optimization of particle design and material formulation for the development of an improved oral delivery system for protein drugs.
    Matched MeSH terms: Delayed-Action Preparations/administration & dosage
  4. Rehman K, Zulfakar MH
    Pharm Res, 2017 01;34(1):36-48.
    PMID: 27620176 DOI: 10.1007/s11095-016-2036-8
    PURPOSE: To characterize bigel system as a topical drug delivery vehicle and to establish the immunomodulatory role of imiquimod-fish oil combination against skin cancer and inflammation resulting from chemical carcinogenesis.

    METHODS: Imiquimod-loaded fish oil bigel colloidal system was prepared using a blend of carbopol hydrogel and fish oil oleogel. Bigels were first characterized for their mechanical properties and compared to conventional gel systems. Ex vivo permeation studies were performed on murine skin to analyze the ability of the bigels to transport drug across skin and to predict the release mechanism via mathematical modelling. Furthermore, to analyze pharmacological effectiveness in skin cancer and controlling imiquimod-induced inflammatory side effects, imiquimod-fish oil combination was tested in vitro on epidermoid carcinoma cells and in vivo in Swiss albino mice cancer model.

    RESULTS: Imiquimod-loaded fish oil bigels exhibited higher drug availability inside the skin as compared to individual imiquimod hydrogel and oleogel controls through quasi-Fickian diffusion mechanism. Imiquimod-fish oil combination in bigel enhanced the antitumor effects and significantly reduced serum pro-inflammatory cytokine levels such as tumor necrosis factor-alpha and interleukin-6, and reducing tumor progression via inhibition of vascular endothelial growth factor. Imiquimod-fish oil combination also resulted in increased expression of interleukin-10, an anti-inflammatory cytokine, which could also aid anti-tumor activity against skin cancer.

    CONCLUSION: Imiquimod administration through a bigel vehicle along with fish oil could be beneficial for controlling imiquimod-induced inflammatory side effects and in the treatment of skin cancer.

    Matched MeSH terms: Delayed-Action Preparations/administration & dosage*
  5. Sheshala R, Quah SY, Tan GC, Meka VS, Jnanendrappa N, Sahu PS
    Drug Deliv Transl Res, 2019 04;9(2):434-443.
    PMID: 29392681 DOI: 10.1007/s13346-018-0488-6
    The objectives of present research were to develop and characterize thermosensitive and mucoadhesive polymer-based sustained release moxifloxacin in situ gels for the treatment of periodontal diseases. Poloxamer- and chitosan-based in situ gels are in liquid form at room temperature and transform into gel once administered into periodontal pocket due to raise in temperature to 37 °C. Besides solution-to-gel characteristic of polymers, their mucoadhesive nature aids the gel to adhere to mucosa in periodontal pocket for prolonged time and releases the drug in sustained manner. These formulations were prepared using cold method and evaluated for pH, solution-gel temperature, syringeability and viscosity. In vitro drug release studies were conducted using dialysis membrane at 37 °C and 50 rpm. Antimicrobial studies carried out against Aggregatibacter actinomycetemcomitans (A.A.) and Streptococcus mutans (S. Mutans) using agar cup-plate method. The prepared formulations were clear and pH was at 7.01-7.40. The viscosity of formulations was found to be satisfactory. Among the all, formulations comprising of 21% poloxamer 407 and 2% poloxamer 188 (P5) and in combination with 0.5% HPMC (P6) as well as 2% chitosan and 70% β-glycerophosphate (C6) demonstrated an ideal gelation temperature (33-37 °C) and sustained the drug release for 8 h. Formulations P6 and C6 showed promising antimicrobial efficacy with zone of inhibition of 27 mm for A.A. and 55 mm for S. Mutans. The developed sustained release in situ gel formulations could enhance patient's compliance by reducing the dosing frequency and also act as an alternative treatment to curb periodontitis.
    Matched MeSH terms: Delayed-Action Preparations/administration & dosage
  6. Meka VS, Murthy Kolapalli VR
    Curr Drug Deliv, 2016;13(6):971-81.
    PMID: 26452534
    A central composite design was applied to design a novel gastric floating drug delivery system comprising propranolol HCl in Terminalia catappa gum and to evaluate the buoyancy, in vitro drug release behavior, and pharmacokinetic parameters. All formulations exhibited good buoyancy properties in vitro reflected by floating lag time of 1-110 sec, total floating time of 9-16 h and prolonged release behaviour (upto 12 h). Statistically optimised formulation (PBGRso) was orally administered to human volunteers under both fasted and fed conditions to evaluate gastric floating behavior under different food conditions by X-ray evaluation. In vivo studies of optimised formulations revealed that the gastric residence time of floating tablets was enhanced in the fed but not in the fasted state. Pharmacokinetic studies of the optimised Terminalia catappa formulation and a commercial product (Ciplar LA 80) carried out on healthy human volunteers showed a significant improvement in the bioavailability (132%) of propranolol HCl released from from the experimental Terminalia catappa formulations compared with Ciplar LA 80.
    Matched MeSH terms: Delayed-Action Preparations/administration & dosage*
  7. Shahid N, Siddique MI, Razzaq Z, Katas H, Waqas MK, Rahman KU
    Drug Dev Ind Pharm, 2018 Dec;44(12):2061-2070.
    PMID: 30081679 DOI: 10.1080/03639045.2018.1509081
    OBJECTIVE: This study was designed to optimize and develop matrix type transdermal drug delivery system (TDDS) containing tizanidine hydrochloride (TZH) using different polymers by solvent evaporation method.

    SIGNIFICANCE: A strong need exists for the development of transdermal patch having improved bioavailability at the site of action with fewer side effects at off-target organs.

    METHODS: The patches were physically characterized by texture analysis (color, flexibility, smoothness, transparency, and homogeneity), in vitro dissolution test and FTIR analysis. Furthermore, functional properties essential for TDDS, in vitro percentage of moisture content, percentage of water uptake, in vitro permeation by following different kinetic models, in vivo drug content estimation and skin irritation were determined using rabbit skin.

    RESULTS: The optimized patches were soft, of uniform texture and thickness as well as pliable in nature. Novel transdermal patch showed ideal characteristics in terms of moisture content and water uptake. FTIR analysis confirmed no interaction between TZH and cellulose acetate phthalate (CAP). The patch showed sustained release of the drug which increased the availability of short acting TZH at the site of action. The patch also showed its biocompatibility to the in vivo model of rabbit skin.

    CONCLUSIONS: The results demonstrated that topically applied transdermal patch will be a potential medicated sustain release patch for muscle pain which will improve patient compliance.

    Matched MeSH terms: Delayed-Action Preparations/administration & dosage
  8. Springer SA, Di Paola A, Barbour R, Azar MM, Altice FL
    J Acquir Immune Defic Syndr, 2018 09 01;79(1):92-100.
    PMID: 29781884 DOI: 10.1097/QAI.0000000000001759
    OBJECTIVE: To determine whether extended-release naltrexone (XR-NTX) would improve or maintain viral suppression (VS) among incarcerated individuals with HIV and alcohol use disorders (AUDs) transitioning to the community.

    DESIGN: A randomized, double-blind, placebo-controlled trial was conducted among incarcerated individuals with HIV and AUDs transitioning to the community from 2010 through 2016.

    METHODS: Eligible participants (N = 100) were randomized 2:1 to receive 6 monthly injections of XR-NTX (n = 67) or placebo (n = 33) starting at release and continued for 6 months. The primary and secondary outcomes were the proportion that maintained or improved VS at <200 and <50 copies per milliliter from baseline to 6 months, respectively, using an intention-to-treat analysis.

    RESULTS: Participants allocated to XR-NTX improved VS from baseline to 6 months for <200 copies per milliliter (48.0%-64.2%, P = 0.024) and for <50 copies per milliliter (31.0%-56.7%, P = 0.001), whereas the placebo group did not (<200 copies/mL: 64%-42.4%, P = 0.070; <50 copies/mL: 42.0%-30.3%, P = 0.292). XR-NTX participants were more likely to achieve VS than the placebo group at 6 months (<200 copies/mL: 64.2% vs. 42.4%; P = 0.041; <50 copies/mL: 56.7% vs. 30.3%; P = 0.015). XR-NTX independently predicted VS [<200 copies/mL: adjusted odds ratio (aOR) = 2.68, 95% confidence interval (CI) = 1.01 to 7.09, P = 0.047; <50 copies/mL: aOR = 4.54; 95% CI = 1.43 to 14.43, P = 0.009] as did receipt of ≥3 injections (<200 copies/mL: aOR = 3.26; 95% CI = 1.26 to 8.47, P = 0.010; <50 copies/mL: aOR = 6.34; 95% CI = 2.08 to 19.29, P = 0.001). Reductions in alcohol consumption (aOR = 1.43, 95% CI = 1.03 to 1.98, P = 0.033) and white race (aOR = 5.37, 95% CI = 1.08 to 27.72, P = 0.040) also predicted VS at <50 copies per milliliter.

    CONCLUSIONS: XR-NTX improves or maintains VS after release to the community for incarcerated people living with HIV and AUDs.

    Matched MeSH terms: Delayed-Action Preparations/administration & dosage*
  9. Haseeb MT, Hussain MA, Bashir S, Ashraf MU, Ahmad N
    Drug Dev Ind Pharm, 2017 Mar;43(3):409-420.
    PMID: 27808567 DOI: 10.1080/03639045.2016.1257017
    CONTEXT: Advancement in technology has transformed the conventional dosage forms to intelligent drug delivery systems. Such systems are helpful for targeted and efficient drug delivery with minimum side effects. Drug release from these systems is governed and controlled by external stimuli (pH, enzymes, ions, glucose, etc.). Polymeric biomaterial having stimuli-responsive properties has opened a new area in drug delivery approach.

    OBJECTIVE: Potential of a polysaccharide (rhamnogalacturonan)-based hydrogel from Linseeds (Linum usitatissimum L.) was investigated as an intelligent drug delivery material.

    MATERIALS AND METHODS: Different concentrations of Linseed hydrogel (LSH) were used to prepare caffeine and diacerein tablets and further investigated for pH and salt solution-responsive swelling, pH-dependent drug release, and release kinetics. Morphology of tablets was observed using SEM.

    RESULTS: LSH tablets exhibited dynamic swelling-deswelling behavior with tendency to swell at pH 7.4 and in deionized water while deswell at pH 1.2, in normal saline and ethanol. Consequently, pH controlled release of the drugs was observed from tablets with lower release (<10%) at pH 1.2 and higher release at pH 6.8 and 7.4. SEM showed elongated channels in swollen then freeze-dried tablets.

    DISCUSSION: The drug release was greatly influenced by the amount of LSH in the tablets. Drug release from LSH tablets was governed by the non-Fickian diffusion.

    CONCLUSIONS: These finding indicates that LSH holds potential to be developed as sustained release material for tablet.

    Matched MeSH terms: Delayed-Action Preparations/administration & dosage*
  10. Wu DB, Lee EH, Chung WS, Chow DP, Lee VW, Wong MC, et al.
    Psychiatry Res, 2013 Dec 30;210(3):745-50.
    PMID: 24012164 DOI: 10.1016/j.psychres.2013.07.012
    Schizophrenia is one of the most expensive psychiatric illnesses. This study compared retrospectively health-care resources consumed 12 months before and 24 months after risperidone long-acting injection (RLAI) treatment in Hong Kong. A mirror-image analysis was conducted using data (N=191) from three public hospitals in Hong Kong from 2003 to 2007. The main outcome measure was hospitalisation cost. Other secondary outcomes such as hospitalisation episodes, outpatient visits and adverse events were also compared. A predictive model was established using linear regression based on generalised estimating equations. Analysis showed that RLAI was associated with a reduction in hospitalisation cost by HK$10,001,390 (24.7%) (HK$40,418,694 vs. HK$30,417,303; P-value <0.05). Days of hospitalisation were reduced by 1538 days (10.1%) (15,271 vs. 13,733; P-value <0.05). The predictive model estimated that the hospitalisation cost of patients using RLAI was only 11.1% (3.1-3.93%, 95% confidence interval (CI)) compared to those receiving conventional antipsychotics combined with oral risperidone. Cost of hospitalisation was significantly reduced after RLAI therapy. However, results should be considered as indicative or suggestive only, due to potential channelling bias where certain drug regimens are preferentially prescribed to patients with particular conditions. The findings from our study may be useful in health-care decision making considering treatment options for schizophrenia in resource-limited settings.
    Matched MeSH terms: Delayed-Action Preparations/administration & dosage*
  11. Saifullah B, Hussein MZ, Hussein Al Ali SH
    Int J Nanomedicine, 2012;7:5451-63.
    PMID: 23091386 DOI: 10.2147/IJN.S34996
    Tuberculosis (TB), caused by the bacteria Mycobacterium tuberculosis, is notorious for its lethality to humans. Despite technological advances, the tubercle bacillus continues to threaten humans. According to the World Health Organization's 2011 global report on TB, 8.8 million cases of TB were reported in 2010, with a loss of 1.7 million human lives. As drug-susceptible TB requires long-term treatment of between 6 and 9 months, patient noncompliance remains the most important reason for treatment failure. For multidrug-resistant TB, patients must take second-line anti-TB drugs for 18-24 months and many adverse effects are associated with these drugs. Drug-delivery systems (DDSs) seem to be the most promising option for advancement in the treatment of TB. DDSs reduce the adverse effects of drugs and their dosing frequency as well as shorten the treatment period, and hence improve patient compliance. Further advantages of these systems are that they target the disease area, release the drugs in a sustained manner, and are biocompatible. In addition, targeted delivery systems may be useful in dealing with extensively drug-resistant TB because many side effects are associated with the drugs used to cure the disease. In this paper, we discuss the DDSs developed for the targeted and slow delivery of anti-TB drugs and their possible advantages and disadvantages.
    Matched MeSH terms: Delayed-Action Preparations/administration & dosage*
  12. Wilairat P, Kengkla K, Thayawiwat C, Phlaisaithong P, Somboonmee S, Saokaew S
    Chron Respir Dis, 2018 12 19;16:1479973118815694.
    PMID: 30558448 DOI: 10.1177/1479973118815694
    To examine clinical outcomes of theophylline use in patients with chronic obstructive pulmonary disease (COPD) receiving inhaled corticosteroids (ICS) and long-acting beta-2 agonists (LABA). Electronic data from five hospitals located in Northern Thailand between January 2011 and December 2015 were retrospectively collected. Propensity score (PS) matching (2:1 ratio) technique was used to minimize confounding factors. The primary outcome was overall exacerbations. Secondary outcomes were exacerbation not leading to hospital admission, hospitalization for exacerbation, hospitalization for pneumonia, and all-cause hospitalizations. Cox's proportional hazards models were used to estimate adjusted hazard ratio (aHR) and 95% confidence interval (CI). After PS matching, of 711 patients with COPD (mean age: 70.1 years; 74.4% male; 60.8% severe airflow obstruction), 474 theophylline users and 237 non-theophylline users were included. Mean follow-up time was 2.26 years. Theophylline significantly increased the risk of overall exacerbation (aHR: 1.48, 95% CI: 1.11-1.96; p = 0.008) and exacerbation not leading to hospital admission (aHR: 1.47, 95% CI: 1.06-2.03; p = 0.020). Theophylline use did not significantly increase the risk of hospitalization for exacerbation (aHR: 1.11, 95% CI: 0.79-1.58; p = 0.548), hospitalization for pneumonia (aHR: 1.28, 95% CI: 0.89-1.84; p = 0.185), and all-cause hospitalizations (aHR: 1.03, 95% CI: 0.80-1.33; p = 0.795). Theophylline use as add-on therapy to ICS and LABA might be associated with an increased risk for overall exacerbation in patients with COPD. A large-scale prospective study of theophylline use investigating both safety and efficacy is warranted.
    Matched MeSH terms: Delayed-Action Preparations/administration & dosage
  13. Marcus R, Bojko MJ, Mazhnaya A, Makarenko I, Filippovych S, Dvoriak S, et al.
    J Subst Abuse Treat, 2018 03;86:86-93.
    PMID: 29415856 DOI: 10.1016/j.jsat.2018.01.003
    Numerous individual barriers, including negative attitudes toward opioid agonist therapies (OAT), have undermined HIV prevention efforts in Ukraine where the epidemic is concentrated in people who inject drugs (PWID). The recent availability of extended-release naltrexone (XR-NTX), an opioid antagonist, provides new opportunities for treatment and prevention, but little is known about patient preferences. We conducted qualitative analysis using focus groups (FG) of PWID recruited based on OAT experience: currently, previously, and never on OAT in five Ukrainian cities. FG included 199 PWID in 25 focus groups. Focus group transcripts were coded and analyzed using a modified grounded theory approach to identify common themes and domains related to attitudes about and preferences for XR-NTX, relative to other treatments. Interest in XR-NTX was supported if supervised opioid withdrawal and psychological support were assured. Other factors supporting XR-NTX included a focus on younger PWID early in their injection career and motivated for recovery. Perceptions of recovery included not receiving psychoactive medications like methadone or buprenorphine. With more information, XR-NTX could be a viable option for PWID in Ukraine, especially if concerns regarding withdrawal and psychological support are adequately addressed.
    Matched MeSH terms: Delayed-Action Preparations/administration & dosage
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