Percutaneous absorption and Skin accumulation of Lorazepam-Diphenhydramine- Haloperidol Carbopol gel in Porcine Ear Skin.

This study presents the formulation and evaluation of an ABH Carbopol gel containing lorazepam (Ativan®), diphenhydramine hydrochloride (Benadryl®), and haloperidol (Haldol®) for treating chemotherapy-induced nausea and vomiting (CINV) in hospice patients. ABH PLO gel is widely used for this purpose due to its low cost and presumed efficacy. However, previous studies, including one conducted by the authors, have reported insufficient drug absorption from the ABH PLO gel. Here we hypothesized that the ABH Carbopol gel would provide superior percutaneous absorption of the drugs. ABH Carbopol gel was characterized for pH, viscosity, thermal properties, and infrared spectroscopy. The percutaneous absorption and skin retention of the gel was evaluated across porcine ear skin using Franz diffusion cells, and the drug concentrations were determined by high-performance liquid chromatography. The pH of the ABH Carbopol gel was found to be 6.80 ± 0.33, and the retention time of diphenhydramine, haloperidol, and lorazepam were 4.73, 7.11, and 18.69 minutes, respectively. The thermogram of the ABH Carbopol gel indicates the drugs were present in the dissolved state. Based on the flux data, the estimated steady-state concentration (Css) of diphenhydramine, haloperidol, and lorazepam were found to be 44.64 ng/ml, 2.58 ng/ml, and 20.1 ng/ml, respectively. These values were significantly higher than those obtained from the ABH PLO gel. In conclusion, the ABH Carbopol gel provides a promising alternative to the ABH PLO gel for treating CINV in hospice patients. Further studies are required to validate these findings in clinical settings.

Influence of capsule shell composition on the performance indicators of hypromellose capsule in comparison to hard gelatin capsules.

The purpose of this study was to assess the in vitro performances of "vegetable" capsules in comparison to hard gelatin capsules in terms of shell weight variation, reaction to different humidity conditions, resistance to stress in the absence of moisture, powder leakage, disintegration and dissolution. Two types of capsules made of HPMC produced with (Capsule 2) or without (Capsule 3) a gelling agent and hard gelatin capsules (Capsule 1) were assessed. Shell weight variability was relatively low for all tested capsules shells. Although Capsule 1 had the highest moisture content under different humidity conditions, all capsule types were unable to protect the encapsulated hygroscopic polyvinylpyrrolidone (PVP) powder from surrounding humidity. The initial disintegration for all Capsule 1 occurred within 3 min, but for other types of capsules within 6 min (n = 18). Dissolution of acetaminophen was better when the deionized water (DIW) temperature increased from 32 to 42 °C in case of Capsule 1, but the effect of temperature was not significant for the other types of capsules. Acetaminphen dissolution from Capsule 1 was the fastest (i.e. >90% in 10 min) and independent of the media pH or contents unlike Capsule 2 which was influenced by the pH and dissolution medium contents. It is feasible to use hypromellose capsules shells with or without gelling agent for new lines of pharmaceutical products, however, there is a window for capsule shells manufacturing companies to improve the dissolution of their hypromellose capsules to match the conventional gelatin capsule shells and eventually replace them.

An update on the latest strategies in retinal drug delivery.

INTRODUCTION: Retinal drug delivery has witnessed significant advancements in recent years, mainly driven by the prevalence of retinal diseases and the need for more efficient and patient-friendly treatment strategies. AREAS COVERED: Advancements in nanotechnology have introduced novel drug delivery platforms to improve bioavailability and provide controlled/targeted delivery to specific retinal layers. This review highlights various treatment options for retinal diseases. Additionally, diverse strategies aimed at enhancing delivery of small molecules and antibodies to the posterior segment such as implants, polymeric nanoparticles, liposomes, niosomes, microneedles, iontophoresis and mixed micelles were emphasized. A comprehensive overview of the special technologies currently under clinical trials or already in the clinic was provided. EXPERT OPINION: Ideally, drug delivery system for treating retinal diseases should be less invasive in nature and exhibit sustained release up to several months. Though topical administration in the form of eye drops offers better patient compliance, its clinical utility is limited by nature of the drug. There is a wide range of delivery platforms available, however, it is not easy to modify any single platform to accommodate all types of drugs. Coordinated efforts between ophthalmologists and drug delivery scientists are necessary while developing therapeutic compounds, right from their inception.

Community pharmacists' response to complaints of gastroesophageal reflux: A simulated patient study in the Northern United Arab Emirates.

INTRODUCTION: Patients frequently use gastric acid-reducing agents (ARAs) to treat symptoms affecting the gastrointestinal tract. Thus, the risk for drug-drug interactions (DDI) is a serious concern. This potentially makes the community pharmacist (CP) act as a primary intervention by providing the appropriate counseling and dispensing practice. OBJECTIVE: To evaluate CPs' counseling and dispensing practices regarding complaints of Gastroesophageal Reflux Disease (GERD), including recommending an appropriate course of action to prevent possible DDIs. MATERIALS AND METHODS: A simulated patient (SP) methodology was used in this study. The community pharmacies in Ajman and Sharjah were visited by SP who's responsible for acting as a patient, and by an observer who's responsible for focusing on the interaction between the SP and the CPs without engagement. Data were recorded using a preprepared data collection form. Performance feedback was sent to the CPs after concluding all visits. Counseling and dispensing scores were classified based on the total scores to poor, inadequate, and complete. Appropriateness of the pharmacist's decision was defined as dispensing antacid and advising of separating doses apart in time. RESULTS: A total of 150 community pharmacies was included in the data analysis. The findings of the current study demonstrated poor counseling and dispensing for the vast majority of the participants (81.3% and 67.3% of respondents, respectively). Only 4% of the CPs advised the SP to have a time interval between antacid and cefuroxime axetil. A significant difference in counseling scores was found between pharmacies located in Ajman and Sharjah (p = 0.01). Also, there was a significant difference in dispensing scores between independent and chain pharmacies (p = 0.003). CONCLUSIONS: The findings revealed inadequate counseling and dispensing practice by CPs. This study highlighted the need for continuous professional training programs to endow the CPs with the knowledge necessary for improving the CPs' counseling and dispensing practices.

Nanocarriers for the Delivery of Neuroprotective Agents in the Treatment of Ocular Neurodegenerative Diseases.

Retinal neurodegeneration is considered an early event in the pathogenesis of several ocular diseases, such as diabetic retinopathy, age-related macular degeneration, and glaucoma. At present, there is no definitive treatment to prevent the progression or reversal of vision loss caused by photoreceptor degeneration and the death of retinal ganglion cells. Neuroprotective approaches are being developed to increase the life expectancy of neurons by maintaining their shape/function and thus prevent the loss of vision and blindness. A successful neuroprotective approach could prolong patients' vision functioning and quality of life. Conventional pharmaceutical technologies have been investigated for delivering ocular medications; however, the distinctive structural characteristics of the eye and the physiological ocular barriers restrict the efficient delivery of drugs. Recent developments in bio-adhesive in situ gelling systems and nanotechnology-based targeted/sustained drug delivery systems are receiving a lot of attention. This review summarizes the putative mechanism, pharmacokinetics, and mode of administration of neuroprotective drugs used to treat ocular disorders. Additionally, this review focuses on cutting-edge nanocarriers that demonstrated promising results in treating ocular neurodegenerative diseases.

Recent Advancements in Electrospun Nanofibers for Wound Healing: Polymers, Clinical and Regulatory Perspective.

Wound management is an unmet therapeutic challenge and a global healthcare burden. Current treatment strategies provide limited efficiency in wound management, thus undergoing constant evolution in the treatment approaches. As wound healing is a complex physiological process involving precise synchronization of various phases like hemostasis, inflammation and remodelling, which necessitates innovative treatment strategies. Nanotechnology platforms like polymeric nanofibers (NFs) offer a promising solution for wound management. NFs contain a porous mesh-like structure that mimics the natural extracellular matrix and promote the cell adhesion and proliferation in the wound bed, thus displaying a great potential as a wound healing scaffold. Electrospinning is a simple, versatile and scalable technique for producing highly porous and tuneable NFs with a high surface area. Electrospun NFs are presenting extensive application in wound management, especially for burns and diabetic foot ulcers. This review briefly discusses the wound physiology and conventional treatment strategies. It also provides an overview of the electrospinning process and its principle, highlighting the application of electrospun polymeric NFs in wound management. The authors have made an attempt to emphasizes on the clinical challenges and future perspectives along with regulatory aspects of NFs as a wound dressing.

Synthesis, Characterization and Safety Evaluation of Sericin-Based Hydrogels for Controlled Delivery of Acyclovir.

Conventional formulations of antiviral drug acyclovir have various limitations such as low bioavailability. The current study was aimed at developing polymeric matrices for the controlled delivery of acyclovir using sericin as polymer and acrylic acid (AA) as a monomer. The free radical polymerization technique was used for hydrogel formulation. Briefly, sericin was chemically cross-linked with acrylic acid. N'-N'-methylene bis-acrylamide (MBA) and ammonium persulfate (APS) were used as cross-linker and initiator, respectively. FTIR spectra showed that acyclovir was successfully loaded into sericin hydrogel. SEM micrographs revealed that the outer surface was solid-like and smooth. According to DSC thermograms, the developed polymeric network was thermally stable. Amorphous nature of acyclovir was observed in XRD. The pH of medium and reactants' concentration affected swelling dynamics and acyclovir release pattern. In addition, drug release occurred through a diffusion-controlled process. Sericin hydrogel suspension was well tolerable up to 3800 mg/kg of rabbits' body weight. Haematology and serum chemistry results were well within the range signifying normal liver and kidney functions. Similarly, histopathology slides of the rabbit's vital organs were also in normal condition without causing any histopathological change. It was concluded from the findings that sericin-co-AA polymeric matrices are ideal for the pH-dependent delivery of acyclovir.

HPMC capsules: current status and future prospects.

Hydroxypropyl methylcellulose (HPMC) is employed for a wide variety of pharmaceutical and food preparations. Its applications as viscolizing agent (thickening agent), coating polymer, bioadhesive, in solid dispersion to enhance solubility, binder in the process of granulation and in modified release formulations have been well documented. One other notable use is in the production of capsule shells, replacing the animal derived gelatin in conventional two-piece capsules. The aim of this review is to systemically survey published literature on the HPMC use in capsule shells and resolve questions regarding their suitability as a replacement for hard gelatin capsules. Future refinements in the production and filling of HPMC capsule shells and improvement in their in vivo/in vitro dissolution would ensure their superiority over hard gelatin capsules.

In Vitro Dissolution and in Silico Modeling Shortcuts in Bioequivalence Testing.

PURPOSE: To review in vitro testing and simulation platforms that are in current use to predict in vivo performances of generic products as well as other situations to provide evidence for biowaiver and support drug formulations development. METHODS: Pubmed and Google Scholar databases were used to review published literature over the past 10 years. The terms used were "simulation AND bioequivalence" and "modeling AND bioequivalence" in the title field of databases, followed by screening, and then reviewing. RESULTS: A total of 22 research papers were reviewed. Computer simulation using software such as GastroPlus™, PK-Sim® and SimCyp® find applications in drug modeling. Considering the wide use of optimization for in silico predictions to fit observed data, a careful review of publications is required to validate the reliability of these platforms. For immediate release (IR) drug products belonging to the Biopharmaceutics Classification System (BCS) classes I and III, difference factor (ƒ1) and similarity factor (ƒ2) are calculated from the in vitro dissolution data of drug formulations to support biowaiver; however, this method can be more discriminatory and may not be useful for all dissolution profiles. CONCLUSIONS: Computer simulation platforms need to improve their mechanistic physiologically based pharmacokinetic (PBPK) modeling, and if prospectively validated within a small percentage of error from the observed clinical data, they can be valuable tools in bioequivalence (BE) testing and formulation development.

Proper Counseling and Dispensing of Isotretinoin Capsule Products by Community Pharmacists in UAE: A Simulated Patient Study.

PURPOSE: To evaluate the pharmacist's assessment of patient eligibility for safe use of isotretinoin and the quality of pharmacist's counseling. PATIENTS AND METHODS: A covert simulated patient (SP) methodology was used in which a trained female researcher, who was 25 years old, played the patient's role through this cross-sectional study by visiting community pharmacies and requesting isotretinoin capsules through a controlled prescription. A data form was used to collect the information following each pharmacy visit by asking about medical/family history and providing comprehensive counseling about the most common adverse effects, proper use instructions, and the importance of adherence to medication. The pharmacists, who did not initiate counseling, were prompted by the SP. RESULTS: The pharmacists in 400 pharmacies who agreed to participate were visited by the SP. Only 7 (2%) pharmacists provided a complete assessment of patient eligibility for using isotretinoin with comprehensive counseling. Most of the pharmacists (84%) provided incomplete assessment as indicated by the overall score. Only 11 (3%) pharmacists asked the six crucial questions for the assessment of patient eligibility. On prompting, only 6 (2%) pharmacists provided complete counseling about the expected adverse effects. The most frequently provided adverse effect was dry skin, specifically dry lips (71.8%). A minority of 108 (27%) pharmacists provided education about the importance of using contraception during isotretinoin therapy. A complete level of counseling was provided by 125 (31.3%) pharmacists regarding the lab tests that the SP needs to undergo during therapy. Female pharmacists were more likely to provide counseling about the pregnancy test (mean=134, p=0.001). CONCLUSION: Suboptimal level of the patient's assessment was revealed with poor educational counseling by the community pharmacists. New strategies are needed to improve pharmaceutical care services in the UAE.

Evaluation of Cytotoxicity and Taste-Masking Effect of Selected Flavors on Dental Lidocaine HCl Injection.

AIM: Anxiety and intolerance to dental local anesthetic injections are common in patients undergoing dental procedures. This work was designed to study cytotoxicity of selected flavors in primary gingival keratinocytes (PGK), to acquire information on their suitability for use in dental lidocaine hydrochloride (LID) injection. We also evaluated the bio-mimetic taste of LID dental injection in the presence of selected flavors and sweetener using an Astree electronic tongue (ETongue). METHODS: The cytotoxicity of chocolate natural and artificial flavor (CTE), raspberry flavor artificial (RAS), cherry flavor (CHR), bitterness suppressor flavor (BSF) and lemon flavor extract (LFE) at various dilutions (0.16-10% v/v) was carried out in PGK using the live cell morphological analysis and MTT cell cytotoxicity assay. Based on the cytotoxicity data, CTE and RAS were added to Xylocaine® (2%) along with 0.09% sodium saccharin and taste was assessed using an ETongue. RESULTS: After three hours of treatment, a dose-dependent cell death was induced by all flavors compared to the untreated control. BSF was found to be more toxic when compared to other flavors. CTE was found to be less toxic. The mean IC50 values of CTE, RAS, CHR, BSF and LFE in PGK were found to be 9.54, 8.43, 2.21, 0.38 and 4.01 mg/mL. Taste analysis with the ETongue showed a clear taste difference between the control and test formulations containing CTE and RAS flavors along with sodium saccharin. CONCLUSION: CTE and RAS flavors in combination with 0.09% sodium saccharin can achieve a significant taste-masking effect in the dental LID injection.

Assessing hormonal contraceptive dispensing and counseling provided by community pharmacists in the United Arab Emirates: a simulated patient study.

BACKGROUND: Hormonal contraceptive pills have evolved as a common form of contraception worldwide. Pharmacists play a vital role in providing safe and effective access to these medicines. In many developing countries such as the United Arab Emirates (UAE), these medicines are available to the general public without the presentation of a prescription which requires the pharmacist to shoulder responsibility by assessing and educating patients to assure their appropriate use. OBJECTIVES: To evaluate community pharmacists' current practice of dispensing and counseling on hormonal contraceptives. METHODS: Simulated patient methodology was used in this study. A single simulated patient visited community pharmacies requesting an oral contraceptive as per a preplanned scenario. Information from the visits were recorded on a data collection form including: pharmacist assessing patient eligibility to take hormonal contraceptives, selecting the appropriate oral contraceptive, providing complete counseling on how to use the pill, adherence, missed dose handlings and side effects of the medication. The Pharmacist was prompted by the simulated patient to provide the information if they did not provide spontaneous counseling. The quality of pharmacists' counseling was rated and consequently coded as complete, incomplete or poor. RESULTS: A total of 201 community pharmacies were visited. More than 92% of the pharmacists did not ask the simulated patient any question to assess their eligibility to use contraceptives. Twenty three pharmacists (11.4%) selected the proper product. One hundred seventeen (58.2%) of the pharmacists provided spontaneous counseling on how to use the pill, 17 of them had their counsel rated as complete, but none of the pharmacists provided spontaneous counseling regarding adherence or side effects of the medications. On prompting, 10 pharmacists (12%) provided complete counseling regarding how to use oral contraceptives, 14 pharmacists (7.0%) provided complete counseling on adherence and missing dose handling and five pharmacists (2.5%) provided complete counseling about expected side effects. CONCLUSIONS: Pharmacists' practice regarding hormonal contraceptive dispensing and counseling was suboptimal in this study. Areas needing intervention were related to pharmacist assessment of eligibility for oral contraceptive use, choice of optimal oral contraceptive for patient-specific co-morbidities and provision of adequate counseling regarding proper use, adherence and missed dose handlings.

Pharmacovigilance in perspective: drug withdrawals, data mining and policy implications.

Considering that marketed drugs are not free from side effects, many countries have initiated pharmacovigilance programs. These initiatives have provided countries with methods of detection and prevention of adverse drug reactions at an earlier stage, thus preventing harm occurring in the larger population. In this review, examples of drug withdrawals due to effective pharmacovigilance programs have been provided with details. In addition, information concerning data mining in pharmacovigilance, an effective method to assess pharmacoepidemiologic data and detecting signals for rare and uncommon side effects, is also examined, which is a method synchronized with information technology and advanced electronic tools. The importance of policy framework in relation to pharmacovigilance is discussed in detail, and country experiences upon implementation of pharmacovigilance policies is highlighted.

Smoking Patterns and Willingness to Quit: A Cross-sectional Study in Al Ain City, UAE.

BACKGROUND: Tobacco use is the major cause of preventable morbidity and mortality. The main objectives of this study were to identify smokers willing to participate in quit smoking campaigns using social media and to identify smoking habits of everyday smokers in Al Ain City, United Arab Emirates (UAE). RESEARCH DESIGN AND METHODS: Everyday smokers from Al Ain city of the UAE were surveyed in different locations of the city including malls and specialized tobacco-selling shops. They were interviewed using a semi-structured survey and the information was recorded by one assessor. The information gathered included type and frequency of tobacco use, smoking history and habits, quitting history, desire to quit, and the preferred communication platform. RESULT: A total of 412 regular adult smokers were interviewed in which the majority (95%) reported first smoking at or before the age of 28 years. Participants were mainly UAE nationals (33.7%), Egyptians (14.1%), Syrians (12.9%), and Jordanians (10.9%). Manufactured cigarettes were the main form of tobacco consumption (59.5%), and smoking was mainly solitary (56.3%) and at home (26.3%) and coffee shops (24.9%). The majority of interviewed subjects (76.7%; 95% confidence interval [CI]: 72.4%-80.5%) expressed their interest to quit smoking in the future and 55.3% (95% CI: 50.5%-60.2%) were ready to get involved immediately in a smoking cessation program. Of those, 80.3% (95% CI: 74.6%-84.9%) preferred WhatsApp for receiving smoking cessation motivational education. CONCLUSION: The majority of smokers started at younger ages, which warrant the age of smoking restriction to be raised to 29 years instead of 18 years by the health authority. Everyday smokers were aware of the potentially hazardous effects of tobacco smoking and many were willing to accept help to quit smoking that involves the use of WhatsApp.

Evaluation of Bloodletting Cupping Therapy in the Management of Hypertension.

BACKGROUND: Bloodletting cupping therapy (Hijama) is a traditional alternative medicine practiced in different cultures. Claims about the therapeutic efficacy of Hijama in hypertension are contradictory. The aim of this project was to determine if Hijama therapy is beneficial in the treatment of patients with hypertension. MATERIALS AND METHODS: In this retrospective study, 60 files for patients treated for hypertension, aged 40-60 years and whose systolic blood pressure (SBP) is at least 140mm Hg, were used. The data from 30 patient files were obtained from three licensed Hijama centers (study group), whereas data from the rest of 30 patient files were collected from a hospital (control group). The data from Hijama centers included age, date of Hijama therapy, and blood pressure measured before each Hijama session. Both diastolic blood pressure (DBP) and SBP data were obtained over 3-month period. RESULTS: The results showed a significant reduction in SBP (P value < 0.01) over three sessions of wet cupping (from 149.2 to 130.8mm Hg), but this was not significant for DBP over three sessions (P = 0.074). The study also found that the mean SBP in the study group was 9.6mm Hg less than that in the control group (130.8 vs. 140.4mm Hg, P = 0.019), whereas there was no significant difference in DBP between the study group and the control group (87.0 vs. 86.0mm Hg, P = 0.75). CONCLUSIONS: Our study shows clear relationship between Hijama and the reduction and control of SBP in patients with hypertension. Therefore, Hijama can be used as an adjunct to conventional therapy, which may allow downtitration of given doses of antihypertensive drugs. The possible association of SBP reduction by Hijama and pain reduction needs an investigation.

Encapsulation of ketoprofen for controlled drug release.

Ketoprofen particles were encapsulated with polyions and gelatin to control the release of the drug in aqueous solutions. Charged linear polyions and gelatin were alternatively deposited on 6 microm drug microcrystals through layer-by-layer (LbL) assembly. Sequential layers of poly(dimethyldiallyl ammonium chloride) (PDDA) and poly(styrenesulfonate) (PSS) were followed by adsorption of two to six gelatin/PSS bilayers with corresponding capsule wall thicknesses ranging from 41 to 111 nm. The release of Ketoprofen from the coated microparticles was measured in aqueous solutions of pH 1.4, 4.1, and 7.4. The release rate has changed at these different pH values. At pH 7.4 the release rate of Ketoprofen from the encapsulated particles was less by 107 times compared to uncoated Ketoprofen. The results provide a method of achieving prolonged drug release through self-assembly of polymeric shells on drug crystals.

Quality Attributes and In Vitro Bioequivalence of Different Brands of Amoxicillin Trihydrate Tablets.

Bacterial resistance and antibiotic drug effectiveness can be related to administering generic products with a subtherapeutic dose or poor in vivo drug release. The aim of this study was to investigate whether locally marketed amoxicillin tablets have the required chemical and physical attributes, including in vitro bioequivalence performance. Five generic products (T1, T2, T3, T4, and T5) containing combination of amoxicillin trihydrate and potassium clavulanate as 1 g strength present in immediate release tablets were compared to the reference listed drug product Augmentin® (R) for weight variation, friability, resistance to crushing, and chemical content of amoxicillin. Difference (ƒ1) and similarity (ƒ2) factors were calculated to assess in vitro bioequivalence requirements. The tablets from different products have shown compliance with the pharmacopeial requirements of the performed tests. The measured resistance to crushing of tablets did not influence the dissolution time. Three generic products released more than 85% of amoxicillin by the first 15 min as did the reference product and were considered as bioequivalent products. T1 and T4 had ƒ1 values of 16.5% and 25.4% respectively and their ƒ2 values were 44.5 and 34.6 respectively, indicating failure to meet in vitro bioequivalence requirements. Tablet formulations can play an important role in achieving bioequivalence. Independent investigations such as this study serve as an important tool to reveal possible inferior or noncompliant products that may find their way to the market.

Evaluation of Certain Pharmaceutical Quality Attributes of Lisinopril Split Tablets.

Tablet splitting is an accepted practice for the administration of drugs for a variety of reasons, including dose adjustment, ease of swallowing and cost savings. The purpose of this study was to evaluate the physical properties of lisinopril tablets as a result of splitting the tablets either by hand or with a splitting device. The impact of the splitting technique of lisinopril (Zestril® tablets, 20 mg) on certain physical parameters such as weight variation, friability, disintegration, dissolution and drug content were studied. Splitting the tablets either by hand or with a splitter resulted in a minute but statistically significant average weight loss of <0.25% of the tablet to the surrounding environment. The variability in the weight of the hand-split tablet halves was more pronounced (37 out of 40 tablet halves varied by more than 10% from the mean weight) than when using the tablet splitter (3 out of 40 tablet halves). The dissolution and drug content of the hand-split tablets were therefore affected because of weight differences. However, the pharmacopoeia requirements for friability and disintegration time were met. Hand splitting of tablets can result in an inaccurate dose and may present clinical safety issues, especially for drugs with a narrow therapeutic window in which large fluctuations in drug concentrations are undesirable. It is recommended to use tablets with the exact desired dose, but if this is not an option, then a tablet splitter could be used.

Future prospect of insulin inhalation for diabetic patients: The case of Afrezza versus Exubera.

The current review was designed to compare between the insulin inhalation systems Exubera and Afrezza and to investigate the reasons why Exubera was unsuccessful, when Afrezza maker is expecting their product to be felicitous. In January 2006, Pfizer secured FDA and EC approval for the first of its kind, regular insulin through Exubera inhaler device for the management of types 1 and 2 diabetes mellitus (DM) in adults. The product was no longer available to the market after less than two years from its approval triggering a setback for competitive new inhalable insulins that were already in various clinical development phases. In contrary, MannKind Corporation started developing its ultra-rapid-acting insulin Afrezza in a bold bid, probably by managing the issues in which Exubera was not successful. Afrezza has been marketed since February, 2015 by Sanofi after getting FDA approval in June 2014. The results from this systematic review indicate the effectiveness of insulin inhalation products, particularly for patients initiating insulin therapy. Pharmaceutical companies should capitalize on the information available from insulin inhalation to produce competitive products that are able to match the bioavailability of subcutaneous (SC) insulin injection and to deal with the single insulin unit increments and basal insulin requirements in some diabetic patients or extending the horizon to inhalable drug products with completely different drug entities for other indications.

Cellactose a co-processed excipient: a comparison study.

This article describes the differences in compaction properties between microcrystalline cellulose (MCC) and alpha-lactose monohydrate physical mixture, and microcrystalline cellulose co-processed with alpha-lactose monohydrate (Cellactose). The different compaction parameters are not only compared for the pure materials but also for the lubricated powders with magnesium stearate. Magnesium stearate does not facilitate the densification of either the physical mixture or Cellactose during compaction. The difference in tablet relaxation of the physical mixture and Cellactose indicates that the negative effect of the lubricant on the interparticle bonding of Cellactose particles is smaller than the physical mixture particles because after compaction, the structure in the Cellactose tablet is completely different from that in the physical mixture tablet. However, a larger increase in tablet relaxation at a high compression speed was found for both Cellactose and the physical mixture at different lubricant concentrations: 1.0% and 0.0%. Accordingly, the decrease in tablet strength was larger for the physical mixture tablets than for the Cellactose tablets when lubrication was applied. The examination of the tablet strengths of tablets compressed from physical mixtures of different ratios of alpha-lactose monohydrate and MCC proved the positive effect of cellulose on the tensile strength of tablets. Co-processing of MCC with alpha-lactose monohydrate showed extra contribution on the tablet strength of a physical mixture with the same mixing ratio. This extra contribution of Cellactose was attributed only to the interfacial attraction of the particles.