Moawia M. Al-Tabakha

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.

Antimicrobial Prospect of Newly Synthesized 1,3-Thiazole Derivatives

A new series of 1,3-thiazole and benzo[d]thiazole derivatives 10–15 has been developed, characterized, and evaluated for in vitro antimicrobial activity at concentrations of 25–200 μg/mL against Gram+ve organisms such as methicillin-resistant Staphylococcus aureus (MRSA), Gram–ve organisms such as Escherichia coli (E. coli), and the fungal strain Aspergillus niger (A. niger) by the cup plate method. Ofloxacin and ketoconazole (10 μg/mL) were used as reference standards for antibacterial and antifungal activity, respectively. Compounds 11 and 12 showed notable antibacterial and antifungal activities at higher concentrations (125–200 μg/mL), whereas benzo[d]thiazole derivatives 13 and 14 were found to display significant antibacterial or antifungal activity (50–75 μg/mL) against the Gram+ve, Gram–ve bacteria, or fungal cells used in the present study. In addition, a correlation between calculated and determined partition coefficient (log P) was established which allows future development of compounds within this series to be carried out based on calculated log P values. Moreover, compounds 13 and 14 show that the optimum logarithm of partition coefficient (log P) should be around 4.

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 α-lactose monohydrate physical mixture, and microcrystalline cellulose co-processed with α-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 α-lactose monohydrate and MCC proved the positive effect of cellulose on the tensile strength of tablets. Co-processing of MCC with α-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.

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

Abstract 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.

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.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.

Effect of the Lubricant Magnesium Stearate on Changes of Specific Surface Area of Directly Compressible Powders under Compression = تأثير المشحم ( مغنيسيوم ستياريت ) على تغيرات المساحة السطحية الخاصة بالمساحيق القابلة للكبس أثناء عملية الكبس

During compression, powders fragment, plastically deform, and/or may behave both ways. Different profiles of specific surface area changes have been shown in several studies for many powders. In this study, the effect of a lubricant on the specific surface area of a powder was studied during the consolidation process of the powder as an attempt to clarify the behavior of powders under compression. Changes in specific surface areas of Starch (Rice starch), cellulose (Avicel ® PH102), spray dried lactose (Zeparox ® ), and dibasic calcium phosphate (Emcompress ® ) were studied using gas adsorption technique. Magnesium stearate was used as a lubricant. Specific surface area of plastically deforming materials; cellulose, and starch was clearly affected by the addition of lubricants. Spray dried lactose combined both fragmenting and plastically deforming behavior in its consolidation under compression and its specific surface area was slightly affected by the addition of lubricant. Specific surface area of fragmenting material; Dibasic calcium phosphate was not affected by the addition of a lubricant.

Novel N-phenylcarbamothioylbenzamides with anti-inflammatory activity and prostaglandin E2 inhibitory properties

A number of 2-((4-ethylphenoxy)methyl)-N-(substituted-phenylcarbamothioyl) benzamides (1a–h) were synthesized via reaction of 2-((4-ethylphenoxy)methyl)benzoyl isothiocyanate (2) as a key intermediate with several substituted primary aromatic amines. The new compounds were characterized by proton nuclear magnetic resonance (1H-NMR), carbon-13 nuclear magnetic resonance (13C-NMR), infrared spectrometry (IR), mass spectrometry (MS), and elemental analysis. The anti-inflammatory activity of 1a–h was investigated by acute carrageenan-induced paw edema in mice using the reference drug indomethacin. The results obtained indicated that, of the derivatives developed, 1a and 1d–h exhibited significantly higher anti-inflammatory activity (26.81%–61.45%) when compared with the reference drug indomethacin (22.43%) (P = 0.0490 for 1a, 0.0015 for 1d, 0.0330 for 1f, and P < 0.001 for 1e and 1h). Moreover, the ulcer incidence of 20% for 1e and 1h was clearly lower when compared with the indomethacin group (in which the ulcer incidence was 80%). Of particular note, the ulcer index of 0.2 for 1e was significantly less than that in the indomethacin group (0.6, P = 0.014). Additionally, prostaglandin E2 (PGE2) inhibitory properties were found to be high with 1e (68.32 pg/mL), significantly different from those of the placebo group (530.13 pg/mL, P < 0.001), and equipotent to the effect observed in the indomethacin-pretreated group (96.13 pg/mL, P > 0.05). Moreover, the PGE2 level of 54.15 pg/mL with 1h was also significantly different from that of the placebo group (P < 0.001) and of the indomethacin group (P < 0.05). The significant inhibition of PGE2 observed with 1e (68.32 pg/mL) and 1h (54.15 pg/mL) agree with their observed ulcer incidences. Our overall findings for N-phenylcarbamothioylbenzamides 1a–h clearly suggest that the compounds exhibit an anti-inflammatory effect, potently inhibit PGE2 synthesis, and markedly demonstrate low ulcer incidence.

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.

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 (f1) and similarity (f2) 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 f1 values of 16.5% and 25.4% respectively and their f2 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.