Interactions and incompatibilities of pharmaceutical excipients with active pharmaceutical ingredients: a comprehensive review

Studies of active drug/excipient compatibility represent an important phase in the preformulation stage of the development of all dosage forms. The potential physical and chemical interactions between drugs and excipients can affect the chemical nature, the stability and bioavailability of drugs and, consequently, their therapeutic efficacy and safety. The present review covers the literature reports of interaction and incompatibilities of commonly used pharmaceutical excipients with different active pharmaceutical ingredients in solid dosage forms. Examples of active drug/excipient interactions, such as transacylation, the Maillard browning reaction, acid base reactions and physical changes are discussed for different active pharmaceutical ingredients belonging to different therapeutic categories viz antiviral, anti-inflammatory, antidiabetic, antihypertensive, anti-convulsant, antibiotic, bronchodialator, antimalarial, antiemetic, antiamoebic, antipsychotic, antidepressant, anticancer, anticoagulant and sedative/hypnotic drugs and vitamins. Once the solid-state reactions of a pharmaceutical system are understood, the necessary steps can be taken to avoid reactivity and improve the stability of drug substances and products

Preparation and In Vitro Evaluation of Budesonide Spray Dried Microparticles for Pulmonary Delivery

The present study describes development and in vitro evaluation of budesonide microparticles prepared by spray drying for delivering drug directly to lungs via dry powder inhaler. This paper introduces new formulations for pharmaceutical applications which includes conventional formulations and novel spray dried microparticles viz., pulmosols, microspheres and porous particles. Optimized spray drying parameters for generation of microparticles were: inlet temperature, 130 °C; outlet temperature, 80 °C; aspirator rate, 240 mWc (60%); solution feed rate, 2 ml/min; spraying air flow pressure, 2 bar. Microparticles appeared to be spherical, low-density particles characterized by smooth surface. MMAD and GSD ranged from 2.5–4.6 μm and 1.5–2.7 respectively. Effective index of microspheres (54.48) and porous particle formulations (64.22) was higher than the conventional formulation (49.21) indicating more effective deposition of microparticles to the lungs. Carr’s Index (20–30%) and Hausner ratio (1.2–1.7) for all formulations indicated good powder flow properties. Formulations emitted a fine particle fraction of 25–47%. Microparticles showed extended in vitro drug release upto 4 hours with high respirable fractions, thus use of microparticles potentially offers sustained release profile along with improved delivery of drug to the pulmonary tract

Linear adamantinoid basal cell carcinoma in the axilla

We present a case of asymptomatic deeply pigmented linear plaque with rolled borders that we encountered in an elderly Indian male over a sun protected site, the left axilla. The diagnosis of linear adamantinoid basal cell carcinoma was confirmed on histopathological examination

Linear adamantinoid basal cell carcinoma in the axilla

We present a case of asymptomatic deeply pigmented linear plaque with rolled borders that we encountered in an elderly Indian male over a sun protected site, the left axilla. The diagnosis of linear adamantinoid basal cell carcinoma was confirmed on histopathological examination

Intraventricular empyema caused by Neisseria meningitidis

Meningitis is defined as an inflammation of the protective covering of brain and spinal cord collectively called as meninges. Meningeal infection can be complicated by intraventricular empyema. There are 9 cases of intraventricular empyema described in the literature out of which only three are described to be caused by Neisseria meningitidis. We report the fourth rare case.A 61-year-old female with past medical history of diabetes and hypertension presented with the chief complaint of fever with chills and headache of 1-day duration. CT head did not reveal any acute abnormalities. Lumbar puncture was obtained and empiric IV antimicrobial agents were started. CSF analysis showed gram negative diplococci with culture growing Neisseria meningitidis suggesting meningococcal meningitis. Due to persistent headache and lethargy after complicated meningitis was suspected and MRI of brain was obtained which reflected a diagnosis of intraventricular empyema.Pyogenic ventriculitis also known as intraventricular empyema or ependymitis, is a defined as an inflammation of the ependymal lining of the cerebral ventricular system and is characterized by the presence of suppurative fluid in the ventricles. It is a health care associated complication and is often confused with meningitis due to the similar presentation. Therefore, persistent symptoms despite optimal antimicrobial therapy (therapeutic failure) should alarm the presence of pyogenic ventriculitis.This is the fourth case of intraventricular empyema reported secondary to Neisseria meningitidis. Our case reiterates that clinicians should maintain an index of suspicion for complicated meningitis in patients not responding to standard antimicrobial therapy. Keywords: Ventriculitis, Neisseria meningitidis, Intraventricular empyem

Evaluation of total lymphocyte count (TLC) as a surrogate marker for CD4 count in HIV-positive patients for resource-limited settings

Context: The immunity in HIV-infected patients becomes low due to involvement of CD4 cells. The single best predictor of AIDS onset identified is the percentage or absolute number of circulating CD4+ T cells. However, providences in resource-constraint settings may not have access to this laboratory measurement, or its cost may be prohibitive resulting in the need for an alternative, surrogate marker. Hence, total lymphocyte count (TLC) was evaluated as a probable surrogate marker for CD4 count in this study. Aims: To evaluate the correlation of CD4 counts with the TLC for predicting the progression of HIV infection, and to determine a range of TLC cut-offs for predicting CD4 count <200 cells/μl, which is important for the initiation of antiretroviral therapy (ART) and opportunistic infection (OI) prophylaxis. Settings and Design: This study was conducted in the Department of Microbiology at Government Medical College, Aurangabad. Materials and Methods: A total of 250 HIV-positive patients were included in the study. Their Complete Blood count and CD4 count were measured and the TLC was computed. Statistical Analysis Used: SPSS software version 10.0. Results: A positive correlation between TLC and CD4 count was observed in our study, highlighting the role of this surrogate marker in resource-limited settings. Further, a TLC cut-off of ≤1700 cells/μl was found to be the best predictor for a CD4 count <200 cells/μl. Conclusions: A general correlation between the surrogate marker TLC and expensive CD4 counts could be elicited for the population under study. A TLC cut-off of ≤1700 cells/μl was the best predictor of CD4 count <200 cells/μl. This study demonstrates the ability of TLC, whether used as a continuous or dichotomous data, to predict CD4 count or a CD4 count <200 cells/μl, respectively