3D printing of immediate-release tablets containing olanzapine by filaments extrusion.

In this work, hot-melt extrusion (HME) is coupled with fused deposition modeling (FDM) mediated 3D printing to demonstrate additive manufacturing to fabricate immediate release (IR) prototypes of olanzapine with the aim of enhanced solubility using a fast disintegrating polymer (Kollicoat® IR). Drug-polymer solubility and interaction parameters were estimated by Hansen solubility parameters and Hildebrand-Scott equation. The obtained values signified drug-polymer miscibility. The detailed in vitro physicochemical evaluations of the developed filament through HME and its derived 3D printed tablet by FDM technique were assessed thoroughly by several analytical means such as light microscopy, DSC, XRD, FT-IR, SEM, etc. The average disintegration time of this developed 3D printed IR tablet was found to be 63.33 (±3.6) sec complying with the USP limit. Additionally, in vitro dissolution study data revealed almost close correlations and both showed 100% of drug release within 15 min, thus complying with the definition of IR tablet. Thus, this study demonstrates the feasibility of directly using olanzapine-Kollicoat® IR through the HME process without the addition of any plasticizers, organic solvents, etc. and coupling of HME with 3D printing technology allowing prototypes of IR tablet of olanzapine.

Acute Poisoning with Dapsone and Olanzapine: Severe Methemoglobinemia and Coma with a Favourable Outcome.

Dapsone is a drug commonly used in the treatment of leprosy. In Europe it is rarely prescribed, mostly for the treatment of skin diseases such as dermatitis herpetiformis. Poisoning with dapsone is rare and reports of such cases are of interest for toxicological practice. We describe the only acute dapsone poisoning in a caseload series of 21,000 intoxications treated in the Clinical Toxicology Clinic at St George University Hospital in Plovdiv, Bulgaria between 1999 and 2013. We report on a 36-year-old woman who attempted deliberate self-poisoning with an ingestion of approximately 4.5 g of dapsone and 0.3 g of olanzapine. On admission, the patient was in a state of severe intoxication and comatose. On admission to hospital 9 hours after the ingestion, the methemoglobin level was 51.7%. The patient recovered 8 days later. She received complex treatment including intubation, ventilation, repeated gastric lavage, hemodialysis, blood exchange transfusion and antidote treatment with methylene blue. She was discharged in good clinical condition with minimal organ damage such as mild toxic hepatitis.

The influence of drug physical state on the dissolution enhancement of solid dispersions prepared via hot-melt extrusion: a case study using olanzapine.

In this study, we examine the relationship between the physical structure and dissolution behavior of olanzapine (OLZ) prepared via hot-melt extrusion in three polymers [polyvinylpyrrolidone (PVP) K30, polyvinylpyrrolidone-co-vinyl acetate (PVPVA) 6:4, and Soluplus® (SLP)]. In particular, we examine whether full amorphicity is necessary to achieve a favorable dissolution profile. Drug­polymer miscibility was estimated using melting point depression and Hansen solubility parameters. Solid dispersions were characterized using differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy. All the polymers were found to be miscible with OLZ in a decreasing order of PVP>PVPVA>SLP. At a lower extrusion temperature (160°C), PVP generated fully amorphous dispersions with OLZ, whereas the formulations with PVPVA and SLP contained 14%-16% crystalline OLZ. Increasing the extrusion temperature to 180°C allowed the preparation of fully amorphous systems with PVPVA and SLP. Despite these differences, the dissolution rates of these preparations were comparable, with PVP showing a lower release rate despite being fully amorphous. These findings suggested that, at least in the particular case of OLZ, the absence of crystalline material may not be critical to the dissolution performance. We suggest alternative key factors determining dissolution, particularly the dissolution behavior of the polymers themselves.

Delusional infestation: a clinical profile.

OBJECTIVE: Delusional infestation or delusional parasitosis is a form of monodelusional disorder, a condition sometimes encountered in psychiatric or primary care practice. The outcome of this condition is good when compliance can be ensured. PATIENTS AND METHODS: In the present study, a series of 50 consecutive cases of delusional infestation is reported. RESULTS: A majority of cases (94%) had insidious onset. The duration of symptoms in all but 3 cases was 6 months or more. Twenty-eight cases presented with a delusion of infestation by insects over the body and 20 cases with a delusion of insects crawling over the scalp. Two cases had associated diabetes mellitus, 3 cases had leprosy, 2 cases had dementia, 5 cases had depression, and 4 cases presented with trichotillomania. Among the second generation antipsychotics, risperidone was used in 12 cases, olanzapine in 9 cases, amisulpride in 7 cases, etc. Thirty-four cases (68%) showed complete remission while receiving pharmacotherapy, 13 cases showed partial improvement, and 3 cases did not respond to treatment. CONCLUSIONS: The study demonstrates the utility of second generation antipsychotics in the treatment of this disorder. Further studies are warranted to study the treatment and outcome of this important psychiatric disorder.